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Accueil > Départements > Microbiologie > Micro News

LES NOUVELLES DU DEPARTEMENT DE MICROBIOLOGIE

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The key lipopolysaccharide modifications for antibiotic resistance in Escherichia coli.

12 May 2021 - Escherichia coli acquires resistance to polymyxin B upon the activation of two-component systems, but this is at the expense of innate bile acid resistance. The lack of lipopolysaccharide phosphorylation accounts for bile susceptibility and impairs intestinal colonization in mice
The surface properties of bacterial cells play a key role in resistance to various antimicrobial agents. Gram-negative bacteria expose lipopolysaccharides (LPS) on their surface, which can undergo different structural modifications. However, some of these modifications may be beneficial in some circumstances, but detrimental in others.
In this study, published in Frontiers in Microbiology, the team of Thierry Touzé, in collaboration with a team from Institut Pasteur, showed that Escherichia coli cells resist to cationic antimicrobial peptide polymyxin B, one last resort antibiotic, under conditions that simultaneously activate two-component regulatory systems PmrA/B and PhoP/Q. Among a set of modifications, they identified those responsible for this resistance, which occurs on the lipid A moiety (known as the endotoxin) from LPS. The acquisition of polymyxin B resistance came at the expense of loss of innate resistance to deoxycholate, a major component of bile. They provide evidences that bile susceptibility arises from the inhibition of LpxT-dependent modification, which consists in lipid A phosphorylation. Bile acids are abundant in the small intestine, where they modulate the commensal flora and the researchers further showed that the inactivation of lpxT impaired gut colonization in mice.
These results highlight the importance of lipid A decorations and their tight regulation in the lifestyle of E. coli and probably other Enterobacteriaceae that exhibit the same modifications

Original title : LpxT-Dependent Phosphorylation of Lipid A in Escherichia coli Increases Resistance to Deoxycholate and Enhances Gut Colonization
https://www.frontiersin.org/articles/10.3389/fmicb.2021.676596/full
Contact : Thierry Touzé : thierry.touze i2bc.paris-saclay.fr
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11 May 2021 - Hi ! I’m Sabine Benoist, a Master 1 student in « Integrative Biology and Physiology » at AgroParisTech, following the « plant science » track. I joined the I2BC for a 3 month-stay under the supervision of Benoît Alunni to work on the identification and characterization of new pathogeny factors in the soft rot bacterium Dickeya dadantii. To do so, I will phenotype a set of bacterial mutants on different plant hosts and identify the mutated genes. I’m glad to join this team and to learn with them.

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05 May 2021 - Hi everyone ! My name is Auriane Monestier. I completed my PhD in the “Laboratory of biochemistry” at Ecole Polytechnique, where I focused my research on the formation of the archaeal translation initiation complex. I determined the initiation factor aIF1 role by using especially toeprinting and fluorescence anisotropy. Then, I just finished a post-doctoral fellowship at Micalis institute in GME (Microbial Genetic and Environment) team where I studied the in vivo protein crystallization in Bacillus thuringiensis and the possibility to use its surprising intrinsic capacity to obtain heterologous proteins crystals in vivo.
I am now very glad to join the Dr. Olga Soutourina team and to work with Dr. Johann Peltier and Dr Bruno Dupuy (from Pasteur institute) on a Grant NIH project for a three years post-doctoral fellowship. We aim to understand the role of the Sticklands pathways in the Clostridium difficile colonization and their involvement during co-infection with different Clostridies. I am very excited to start this project and I hope to meet you soon.

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29 April 2021 - Hello, my name is Baptiste and I am a student at the University of Paris Saclay in the second year of a biology degree. I am doing my second year internship with Dr Peltier. I am very happy to have the opportunity to work with Professor Olga Soutourina, Dr Johann Peltier and their team. By adapting the MS2-affinity purification coupled with RNA sequencing technique to C. difficile during my internship, I hope to be able to advance the work of the team by obtaining the targetome corresponding to the sRNA I am studying.

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29 April 2021 - Hello everyone, my name is Lorna Cupit and I am a new intern in the « Regulatory RNAs in Clostridia » team under the supervision of Pr. Olga Soutourina and Dr. Johann Peltier. I am in my 2nd year of my bachelor degree in biology at Paris-Saclay University. For this intership, I am going to work with a PhD student Emma Piattelli on the role of non-coding RNAs in the pathogenesis of Clostridioides difficile. I am looking forward to work with you all ! I will be on your care."

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29 April 2021 - Hi ! My name is Macha Dussouchaud ! After a Bachelor in Life Sciences and Health in Bordeaux, and an exchange semester at the University of Melbourne, I moved to Paris to do my Master in Microbiology. During my internship, I will study with Nicolas Mirouze the regulation of competence in S. aureus. I will particularly help the team to develop a new transcriptional reporter system, involving the luciferase, to study the natural development of competence in this human pathogen. I am pleased to be part of this experience ! See you soon in I2BC !

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28 April 2021 - We congratulate Emma Piattelli, the PhD student from “Regulatory RNAs in Clostridia” team who has just received the two books of Ludovic Orlando as an award for her poster entitled “The role of non-coding RNAs in the pathogenesis of Clostridioides difficile”. It was selected as one of two best posters during the Doctoral School’s “Structure and Dynamics of Living Systems” day held on the 23rd of March. This day is organized every year and is structured as a seminar with regular lectures, posters and a final speech given by Ludovic ORLANDO on "Ancient DNA."

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27 April 2021 - " Hi everyone, my name is Justine Del Bianco. As a student in the Master Course "Biodiversity, Genomic and Environment" of the University Paris-Saclay, I’m a M1 trainee in the team Plant Bacteria Interaction of Peter Mergaert and Denis Faure. I study the impact of the production of the antimicrobial peptide phazolicin by the Rhizobium species Pop5 on interspecific bacterial competition in vitro and in the context of the colonisation of nodules and roots of the legume Phaseolus vulgaris. I’m very happy to join this team for this exciting project. "

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19 April 2021 - Professor Michael DuBow (from Franck Chauvat’s group "Biology and Biotechnology of Cyanobacteria") was named a "Fellow of the Royal Society of Medicine (UK)" in February, 2021. He also continues being a "Fellow of the American Academy of Microbiology", an honor he has had for over 25 years, ever since his election in 1994.
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Impact of Phosphate Availability on Membrane Lipid Content of the Model Strains, Streptomyces lividans and Streptomyces coelicolor.

9 April 2021 - In this paper, we determined how total lipid content of the two model Streptomyces strains, Streptomyces lividans and Streptomyces coelicolor, varies with changes of phosphate (Pi) availability in their culture medium. We demonstrated that the phospholipid content of S. lividans varies considerably with Pi availability, being much lower in Pi limitation than in Pi proficiency, whereas that of S. coelicolor varies little or not. This indicated that the regulation of phosphate metabolism was altered in S. coelicolor. This alteration is likely to be due to the low expression, in this strain, of the two-component PhoR / PhoP system that controls positively phosphate assimilation (https://www.nature.com/articles/s41598-020-65087-w.pdf) .We also characterized an operon, sco0921-20, involved in the biosynthesis of ornithine lipids that are phosphate-free lipids synthesized in replacement of phospholipids in condition of Pi limitation. The biosynthesis of these lipids begins with the N-acylation of ornithine to form lyso-ornithine which is then O-acylated to give ornithine lipid. We demonstrated that SCO0920 has both N- and O-acyltransferase activities whereas SCO0921 has both N-acyltransferase and phospholipase C activities. Our data indicate that in condition of Pi limitation, SCO0921 would specifically degrade phosphatidylinositol to provide missing phosphate to the bacteria


Determination in qRT-PCR of relative expression of genes of the sco0921-0920 and sco1222-1223 operons in S. lividans TK24, its phoP mutant and S. coelicolor M145

Microbiol. 2021 Feb 22 ;12:623919. doi : 10.3389/fmicb.2021.623919. eCollection 2021. PMID : 33692768 Free PMC article
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937720/
Lejeune C, Abreu S, Chaminade P, Dulermo T, David M, Werten S, Virolle MJ
Contact : Marie-Joëlle VIROLLE : marie-joelle.virolle i2bc.paris-saclay.fr
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8 April 2021 - Hi, my name is Ana OLIVEIRA PAIVA and I’m from Portugal. I recently finished my PhD from Leiden University, where I focused my research on the initiation of replication and chromosome remodelling as well as aspects of toxin regulation in C. difficile and tool development. I just started a postdoc with Dr. Johann Peltier in the team of Dr. Olga Soutourina. We aim to unravel the role of the C. difficile L,D-transpeptidases on antibiotic resistance. I’m very excited with the project and hope to meet you all on the upcoming months

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The Phosin PptA Plays a Negative Role in the Regulation of Antibiotic Production in Streptomyces lividans

1 April 2021 - It has long been known that, in Streptomyces, antibiotics biosynthesis is induced in condition of phosphate limitation and therefore repressed in condition of phosphate proficiency. We identified a gene, pptA, whose deletion leads to a dramatic increase of the low antibiotic production of the model strain, Streptomyces lividans. The expression of pptA is induced in condition of phosphate limitation and it encodes a protein possessing a CHAD domain known to constitute a polyphosphate binding module. Polyphosphates are important reservoir of phosphate and energy, mobilized in condition of phosphate limitation or energy stress. We demonstrated the existence of a sharp increase in the abundance of proteins involved in phosphate recovery and transport in the pptA mutant compared to the wild type strain. This indicated that this mutant was suffering phosphate stress and thus that PptA was involved in the degradation of polyphosphates into free phosphate. This gene being very conserved in most sequenced Streptomyces species, its disruption constitutes an interesting strategy to reduce the intracellular phosphate availability and therefore increase antibiotic production in these species.


Antibiotic production of S.lividans TK24 wild type and 3 mutants

Antibiotics 2021, 10(3), 325 ; https://doi.org/10.3390/antibiotics10030325
N. Shikura, E. Darbon, C. Esnault, A. Deniset-Besseau, D. Xu, C. Lejeune, E. Jacquet, N. Nhiri, L. Sago, D. Cornu, S. Werten, C. Martel, M.J. Virolle
Contact : Marie-Joëlle VIROLLE : marie-joelle.virolle i2bc.paris-saclay.fr
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All RNA partners of the Hfq RNA chaperone protein in a human pathogen Clostridioides (Clostridium) difficile

11 March 2021 - During infection, bacteria reprogram the expression of their genes in response to environmental constraints. Non-coding RNAs (ncRNAs) have become important elements of the regulatory networks that control the physiology and virulence of bacterial pathogens. A wide diversity of ncRNAs has been identified in the human enteropathogen Clostridioides (Clostridium) difficile. Some of them interact with the RNA chaperone protein Hfq for their action. Recent analyses have suggested a pleiotropic role of Hfq in C. difficile with the most pronounced effect on sporulation, a key process in the infectious cycle of this pathogen. However, a global view of the RNAs interacting with the Hfq protein in C. difficile was lacking. In the present study, O. Soutourina’s team (Microbiology department, I2BC) with their collaborators at I2BC (Claire Toffano-Nioche, Emilie Drouineau, Daniel Gautheret, Genome Biology department), Institut Pasteur and IBPC in Paris performed RNA sequencing by high throughput immunoprecipitation (RIP-Seq) to identify RNAs associated with Hfq in C. difficile. This work revealed a wide range of mRNAs and ncRNAs interacting with Hfq, including known ncRNAs and potential new regulatory RNAs. New categories of Hfq partner RNAs were identified, including cis antisense RNAs, riboswitches and CRISPR RNAs. The study of one of the ncRNAs associated with Hfq, RCd1, suggests that this RNA contributes to the control of late stages of sporulation in C. difficile. Overall, these data provide an essential molecular basis for exploring the post-transcriptional regulatory network of this enteropathogen.

Title of the original publication : Identification of RNAs bound by Hfq reveals widespread RNA partners and a sporulation regulator in the human pathogen Clostridioides difficile. Boudry P et al. RNA Biology, 2021, DOI : 10.1080/15476286.2021.1882180
https://www.tandfonline.com/doi/full/10.1080/15476286.2021.1882180

contact : [olga.soutourina i2bc.paris-saclay.fr]

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Oxygen transport to gut symbionts

07 March2021 - The insect respiratory system consists of tubular tracheae that transport oxygen to the organs. The tracheal network is dynamic and responds to developmental, environmental and nutritional cues. In a recent article published in the Proceedings of the National Academy of Sciences USA, the Plant Bacteria Interactions team of the Microbiology Department of I2BC, in collaboration with the team of Yoshitomo Kikuchi at the National Institute of Advanced Industrial Science and Technology – Hokkaido in Japan, shows that, in the insect pest Riptortus pedestris, the establishment of an essential symbiosis in the gut with the aerobic bacterial species Burkholderia insecticola triggers the development of an extensive tracheal network enveloping the gut. Genetically blocking the trachea formation prevents this gut symbiosis. We further discovered that the reactive oxygen species-generating enzyme Duox is crucial for the formation and stabilization of tracheae by forming protein cross-links in the tracheal matrix. Reactive oxygen species generated by Duox can be scavenged with antioxidants such as N-acetylcysteine, and feeding insects with this compound prevents tracheal formation and symbiosis. Since many insects obligatorily depend on their symbioses, triggering their collapse by the specific inhibition of the respiratory network with antioxidants could be a new route to fight insect pests.

Confocal image of a gut portion colonized by the symbiont Burkholderia insecticola (green) and enveloped by an extensive tracheal network (yellow).

Title of the publication : Dual oxidase enables insect gut symbiosis by mediating respiratory network formation. Jang et al., 2021. PNAS 2021 Vol. 118 No. 10 e2020922118. https://doi.org/10.1073/pnas.2020922118

contact : peter.mergaert i2bc.paris-saclay.fr

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11 february 2021 - Hi everyone ! My name is Roza Mohammedi. I have a Master degree in Fundamental and Applied Microbiology from the University of Rennes 1 obtained in 2020.
I recently joined the team of Peter Mergaert and Denis Faure as research associate (ingénieur d’étude) with a 13 months contract . I will work on the role phosphorylation signalling cascades during cell cycle and nitrogen fixing symbiosis in Sinorhizobium meliloti. I am very happy to join the team and very excited to work on this project !

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Archaeal Tyrosine Recombinases

10 February 2021 - Integrases belonging to the tyrosine recombinase family are widespread in the three domains of life. These enzymes catalyze the specific recombination between two short DNA segments carried by independent DNA molecules. Among a series of different roles, these enzymes are best known for their capacity to allow integration of mobile genetic elements (MGEs) such as viruses and plasmids into the host chromosome and the reverse reaction of excision. In this FEMS Microbiology Review article, we focused on the integrases encoded by archaea and their mobile elements with a special interest in their peculiar properties not found in bacteria nor eukaryal. Archaea MGEs encode a new class of integrases catalyzing site-specific recombination between a site on the host chromosome and a site residing in their own gene. As a result of the integration event, the integrase gene is disrupted. These enzymes incapable or catalyzing excision after integration have therefore been termed ‘suicidal integrases’. Paradoxically, MGEs encoding these disrupted genes do not disappear. They pervade entire populations by reassembling different fragmented integrase genes and generating new enzymes with different sequence specificities. In addition to their site-specific recombination properties, some of these archaeal enzymes have acquired the capacity to recombine any two DNA segments as long as they share extensive DNA identity. These MGE-encoded enzymes are therefore responsible for intense chromosome rearrangements and the rapid evolution of their archaeal host chromosome

Original title : Archaeal Tyrosine Recombinases
FEMS Microbiol Rev. 2021( open access)
https://academic.oup.com/femsre/advance-article/doi/10.1093/femsre/fuab004/6125969
Contact : jacques.oberto i2bc.paris-saclay.fr
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02 february 2021 - Hello everyone, my name is Clémence Lauden, and I recently joined the BCA team for my M2 internship. I am doing a Master in systematic, evolution palaeontology at Sorbonne University. I have a licence’s degree in ecology from the Paris-Sud University. During my internship, I will work on the evolution of integrases under the direction of Violette Da Cunha and Jacques Oberto. I am excited to work on this project and join the team.

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01 february 2021 -
Hello everyone, my name is Marine Rigot and I newly joined the TrHoGe team for my Master 2 Internship of Microbiology which focus on Microbiotes, pathogens and anti-infectious therapeutics. I have a bachelor’s degree in chemistry-biology from the Paris-Est Créteil university (UPEC). During my Internship I will study the regulation of competence in Staphylococcus aureus under the direction of Nicolas MIROUZE. I’m happy to work on this project and join the team.

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01 february 2021 - Hello everyone, my name is Célia Rizoug Zeghlache and I recently joined the TrHoGe team for my Master 2 internship in microbiology, more specifically on microbiota, pathogens and anti-infectious therapies. I hold a license in Biology and life science from the University of Nîmes (UNIMES). I then did my M1 at the University of Orsay in Health Biology. During my internship I will observe the phenomenon of natural transformation in Staphylococcus aureus by microscopy under the direction of Nicolas MIROUZE. I am happy to be able to participate to this project and to be able to bring my skills to this team

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Soil born Streptomyces solubilize insoluble phosphate for plant nutrition

22 January 2021 -

Some soil-borne microorganisms are known to have the ability to solubilize insoluble rock phosphate and this process often involves the excretion of organic acids. In this issue, we describe the characterization of a novel solubilizing mechanism used by a Streptomyces strain related to Streptomyces griseus isolated from Moroccan phosphate mines. This process involves the excretion of a compound belonging to the viridomycin family that was shown to play a major role in the rock phosphate bio weathering process. We propose that the chelation of the positively charged counter ions of phosphate constitutive of rock phosphate by this molecule leads to the destabilization of the structure of rock phosphate. This would result in the solubilization of the negatively charged phosphates, making them available for plant nutrition. Furthermore, this compound was shown to inhibit growth of fungi and Gram positive bacteria, and this antibiotic activity might be due to its strong ability to chelate iron, a metallic ion indispensable for microbial growth. Considering its interesting properties, this metabolite or strains producing it could contribute to the development of sustainable agriculture acting as a novel type of slow release bio-phosphate fertilizer that has also the interesting ability to limit the growth of some common plant pathogens.

Original title : A Molecule of the Viridomycin Family Originating from a Streptomyces griseus-Related Strain Has the Ability to Solubilize Rock Phosphate and to Inhibit Microbial Growth
Antibiotics 2021, 10(1), 72 ;
https://doi.org/10.3390/antibiotics10010072
Contact : marie-joelle.virolle i2bc.paris-saclay.fr

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Genome-wide identification of novel genes involved in Corynebacteriales cell envelope biogenesis

21 January 2021
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Understanding the biogenesis of Corynebacteriales cell wall is an important challenge because it is essential for the survival of wide spread pathogens such as Mycobacterium tuberculosis and therefore a key target for anti-tuberculosis drugs. In this study, we used a genetic approach based on a genome-wide transposon mutagenesis to identify new players in the assembly of the cell envelope of C. glutamicum, a model organism for all Corynebacteriales species, that has been shown to tolerate dramatic modifications of its cell envelope. We developed an original and efficient screen that allows us to identify as much as 22 new genes potentially involved in C. glutamicum envelope biogenesis. A mutant of particular interest was further characterized and revealed a new player in mycolic acid metabolism. Because a large proportion of these genes is conserved in Corynebacteriales, the library described here, also provides a valuable resource for the whole community working on these bacteria.

Original title : Genome-wide identification of novel genes involved in Corynebacteriales cell envelope biogenesis using Corynebacterium glutamicum as a model
Contact : christine.houssin i2bc.paris-saclay.fr
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0240497

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21 january 2021 - Hello everyone, my name is Emilie LEJAL. After obtaining my Master degree in fundamental microbiology in the Paris-Saclay University in 2016, I spent three years of PhD thesis studying the Microbiota of the tick Ixodes ricinus and its links with tick-borne pathogens presence. I will soon integrate the team of Olga Soutourina : « Regulatory RNAs in Clostridia », for a postdoctoral position aiming to investigate the link between microbiota and diabetes. I am very enthusiastic to work on this new project and to meet you all.

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19 january 2021 - Hello everyone, my name is Abdillah MOHAMED. I obtained a Master in Environment-Host-Microbe Interactions at the University of Montpellier and Pasteur in 2017.
I previously worked in the Integrative Approaches of Ion Transport team, under the supervision of Sébastien THOMINE. We are interested in iron hemostasis in Arabidopsis thaliana, in particular in the identification of genes involved in this process. I recently joined the team of Peter Mergaert and Denis Faure for 12 months.
I will work on the symbiosis between rizobium and legumes such as soybean, under the direction of Benoît ALUNNI. So, I’m excited to work on this project and join the team.

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18 january 2021 - Hello, I’m Aya Yokota and I joined the group of plant-bacteria interactions in January 2021 for a 2 years contract (as an Ingénieur d’étude). After I got my Master degree at the University of Pierre et Marie Curie in Paris, I worked for 3 years in Zurich at the University of Zurich and Agroscope. I’ve been interrested in understanding plant physiological response and later in their interaction with soil microorganisms. I worked on different plant model like A. thaliana, S. lycopersicum (tomato) and L. sativa (lettuce). In this group I will participate in the identification of the genetic determinants for the specific interaction between the bacteria Burkoldheria spp. with its different hosts. I will focus on the interaction between Burkholderia insecticola and the soybean pest Riptortus pedestris. I am very happy to join the institute and excited to work on this new model. I hope to see many of you around !

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Quentin Nicoud, soutiendra sa thèse intitulée "Study of terminal bacteroid differentiation features during the legume-rhizobium symbiosis" le mercredi 03 février à 9h00.

Compte tenu des contraintes sanitaires, la soutenance se déroulera en visioconférence en utilisant le lien suivant : https://eu.bbcollab.com/guest/8d06ae52a698484a9a6623423f49c5dd

Quentin Nicoud a effectué sa thèse dans l’équipe « Interactions Plantes-Bactéries"
https://www.i2bc.paris-saclay.fr/spip.php?article412

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18 january 2021 - Hi. My name is Liliia KHARCHEVSKA and I am inspired by the molecular basis of symbiotic efficiency.
After my Master’s degree in General Biology (Science, Technology, Health ; at Zaporizhzhia National University and Le Mans), I worked as a GMP quality control microbiologist. And this academic year, I continue to deepen my knowledge as an M2 Fundamental Microbiology course student and an intern in the MERGAERT’s Plant-Bacteria Interactions team and at Imagerie-Gif of the I2BC. During my internship, I will work on developing a phenotyping framework to characterize bacteroid physiology in the legume-rhizobium symbiosis through cell biology and biosensor approaches, under the supervision of Benoît ALUNNI and Romain LE BARS. I’m excited to learn and participate in this project, as it will permit to test novel probes and contribute to the understanding of mechanisms that regulate prokaryote-eukaryote interactions.

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15 January 2021

"Antibiotics" : Special Issue "New Potent Antibacterial Agents"

Muriel Masi, member of the team " Bacterial cell envelopes and antibiotics" at the I2BC Institute, is the editor of a special issue of the journal "Antibiotics"

Special Issue Information
Bacteria have developed several mechanisms to circumvent antibiotic activity, causing therapeutic failures. Faced with the worldwide problem of antibiotic resistance, there is an urgent need to discover and develop new antibacterial agents.
In this Special Issue, new potent antibacterial agents with mechanical and structural varieties will be considered as therapeutic approaches to defeat both Gram-positive and Gram-negative pathogens. We will cover the development of new antibiotics resulting from research on medicinal chemistry and synthetic biology, bioactive agents such as bacteriophages and bacteriocins, antibiotic interactions, and adjuvants that target the bacterial lifecycle (such as virulence and communication) or drug resistance mechanisms (such as antibiotic efflux and permeation). All types of articles falling within the scope of the above research areas are welcome.

Deadline for manuscript submissions : 31 June 2021
All Information :
https://www.mdpi.com/journal/antibiotics/special_issues/Potent_Agents

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14 january 2021 - Hello everyone, my name is Victor Folcher and I recently joined the team "Bacterial Envelopes and Antibiotics" for my Master 2 Internship of Fundamental Microbiology. I have a Professional degree in biotechnology and bio-industry from the university Paris-SUD. During my Internship I will study the action mechanism of a bacteriocin targeting the envelope biosynthesis in Enterococcus faecalis. I am excited to work on this project and to learn everything I can.

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15 December 2020

"Antibiotics" : Special Issue "Contexts of Biosynthesis and Functions of the Antibiotics for the Producing Bacteria"

Marie-Joelle VIROLLE, leader of the team " Energetic Metabolism of Streptpmyces" at the I2BC Institute, is the editor of a special issue of the journal "Antibiotics"

Special Issue Information
Antibiotics are often seen as weapons conferring a selective advantage to their producers in a given ecological niche. This prevalent view has prevented the legitimate questioning of the function of the produced antibiotics for the producing bacteria. Therefore, this Special Issue constitutes an attempt to relate the context of antibiotic production to the function of these molecules for its producer, in the specific context of their production. A better understanding of such links is expected to lead to original strategies to enhance the expression of the numerous cryptic pathways present in the genome of the producing bacteria. In consequence, any manuscripts concerning the conditions of antibiotics production and their signaling, the function of the antibiotics produced in a specific environmental/physiological context as well as the reporting of original strategies of “decryptification” of silent pathways are welcome.
1. Conditions of antibiotic production and their signaling ;
2. Different classes of antibiotics, their molecular targets, and their role in the physiology of the bacteria ;
3. Antibiotics as an adaptive response to specific stresses ;
4. Original “decryptification” strategies.
This Special Issue seeks manuscript submissions that will expand and renew our understanding of the triggering of antibiotic biosynthesis by nutritional limitation (crowding/quorum sensing, energetic stress, etc.), the role of antibiotics in programmed cell death, response to oxidative stress, and regulation of energetic metabolism, including the control of respiration and well known inhibition of ATP consuming anabolic processes.

This special issue is now available : https://www.mdpi.com/journal/antibiotics/special_issues/biosyn_anti_bacteria

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09 December 2020 -

Living in the pools of nuclear reactors, some bacteria like it !

The pools of nuclear reactors facilities constitute harsh environments for life, bathed with ionizing radiations, filled with demineralized water and containing toxic radioactive elements. Due to access restrictions and strong handling constraints related to the high radioactivity level, nothing was known about life in water pools directly cooling nuclear cores.
In this work, the French Osiris reactor was investigated. In this open-core reactor, the reactor block is immersed in a pool of water and in communication with it.
The microbial communities present in the Osiris reactor core coolant water were explored during operation and compared with those present at shutdown. Two direct meta-omics approaches, namely DNA metabarcoding and proteotyping, were used. They are respectively based on 16S ribosomal RNA gene sequencing and on peptide analysis.
Against all odds, 25 genera of microorganisms were detected in the extreme environment of a working nuclear core pool, especially the genera Variovorax and Sphingomonas. These genera were supplanted by Methylobacterium, Asanoa, and Streptomyces during shutdown.


The presence of a Variovorax strain in abundance during the reactor operation might be related to its ability to utilize dihydrogen produced during the working cycle. Actually, high energy radiations emitted by the burning fuel generate enormous amounts of dihydrogen through water radiolysis. Moreover, to counter the radiative and metallic stress, Variovorax has been shown to possess multiple metal resistance elements as well as elements involved in antioxidant response.

This finding breaks new ground in the discovery of radioresistant species and in the understanding of the radiotolerance mechanisms that could be exploited in medicine, in radionuclide bioremediation in the environment or in nuclear installations, and in space programmes.

Contact : corinne.rivasseau i2bc.paris-saclay.fr
Original article : Direct meta-analyses reveal unexpected microbial life 3 in the highly radioactive water of an operating 4 nuclear reactor core. Microorganisms 2020, 8

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- - - - - - - — Special issues Editors- - - - - - - - - - - -

09 December 2020

"Pathogens" : Special Issue "Sepsis and Immune Response in Critically Ill Children and Newborn"

Pierre Tissières , leader of the team "Endotoxins, Structures and Host responses" at the I2BC Institute, is the editor of a special issue of the journal "Pathogens".

Special Issue Information
Evolving understanding of sepsis pathophysiology enlights the importance of host responses to pathogens and underlying immunity. In children and infants, immunological transition markedly impacts susceptibility to pathogens and efficacy of the host response to infections. The purpose of this special thematic issue is to review current knowledge’s on pediatric immune response and emerging concepts in critically ill children and infants with sepsis. Although focused on the pediatric field, most recent concepts will be enlarged to sepsis/post aggressive induced immunosuppression, early life immunity transition and impact on neonatal sepsis, critically ill children immunomonitoring and immune failure, sepsis and multisystem inflammatory syndromes phenotypes.

Deadline for manuscript submissions : 31 March 2021
All Information : https://www.mdpi.com/journal/pathogens/special_issues/Sepsis_Immune_Response_Children_Newborn

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"Microorganisms" : Special Issue "Gene Analysis in Bacillus subtilis"

Nicolas Mirouze, leader of the team " Horizontal Gene Transfer in pathogenic bacteria : from old to new model organisms" at the I2BC Institute, is the editor of a special issue of the journal "Microorganisms".

Special Issue Information
Bacillus subtilis is an important model organism for the study of Gram-positive bacteria thanks to its phylogenetic proximity with important human pathogens, its ability to induce important environmental adaptations, its use in the industry, and the numerous genetic tools available.
This Special Issue offers the opportunity to share recent advances in gene analysis in B. subtilis from chromosome organization, to new genes acquisitions (by horizontal gene transfer, for example), to the expression/regulation/function of genes. This Special Issue will also consider advances in synthetic biology and metabolic engineering in B. subtilis.

Deadline for manuscript submissions : 30 July 2021.
All Information :
https://www.mdpi.com/journal/microorganisms/special_issues/Gene_Anal_in_Bacillus_subtilis

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"Microorganisms" : Special Issue "Dickeya and Pectobacterium : Ecology, Pathology and Plant Protection"

Denis Faure, leader of the team " Plant-Bacteria Interactions" at the I2BC Institute, is the editor of a special issue of the journal "Microorganisms" .

Special Issue Information
Pectinolytic enterobacteria Dickeya and Pectobacterium represent a threat for plant and seed production and trade around the world. This Special Issue offers the opportunity to share recent advances in ecology, evolution, taxonomy and pathogenesis of bacteria of the Pectobacterium and Dickeya genera. This Special Issue will also consider advances in diagnosis and biocontrol approaches and plant breeding to limit propagation of these pathogens and their damage on plants.

Deadline for manuscript submissions : 30 June 2021.
All Information : https://www.mdpi.com/journal/microorganisms/special_issues/Dickeya_Pectobacterium

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09 December 2020 - Role of type I Toxin-antitoxin systems in the human pathogen Clostridioides difficile

Toxin-antitoxin (TA) systems are widespread in prokaryotes and encode a stable toxin component and an unstable antitoxin to repress the function or expression of the toxin. The toxin is always of a protein nature while the antitoxin can be a protein or a non-coding RNA. In type I TA systems, the antitoxin is a small antisense RNA that base-pairs with the toxin-encoding mRNA altering its stability and/or translation. The overexpression of toxin inhibits growth or induces cell death while antitoxin protects cells from the toxin’s action.

TA loci were initially discovered on plasmids where they confer stability of maintenance. TA modules were later found in great numbers on bacterial and archaeal chromosomes but their function remains largely unclear. If deregulated those multiple TA modules could even kill their host. How do bacteria manage this potential for self-destruction and stay alive ? Are chromosomal TA modules involved in prophage maintenance, preventing of phage infection, stress response and persister formation ? Could TA modules be just « selfish » DNA elements that promote their propagation within bacterial genomes at the expense of their host ?

Among emerging human enteropathogens, Clostridioides (previous name Clostridium) difficile attracted the attention of the scientific community due to increased incidence and severity of infections and high rate of recurrences. This bacterium has been renamed several times keeping the « difficile » adjective that highlights original difficulties for this bacterium isolation, growth requiring strictly anaerobic conditions and genetic tool limitations.

In the recent paper (Peltier et al. Communications Biology 2020), O. Soutourina team (“Regulatory RNAs in Clostridia”, I2BC Microbiology department) with collaborators describe the identification of five type I TA modules highly conserved within C. difficile prophage regions and provide experimental evidence of their contribution to the stability of these genomic regions. This paper is the result of a collaborative effort of the international teams combining the complementary skills in bacterial genetics, phage and RNA biology (C. difficile phage experts Louis-Charles Fortier and Julian Garneau, Sherbrooke University, Canada ; antisense RNA expert Eliane Hajnsdorf, IBPC, Paris).

Until now a total of 13 potential type I TA modules could be found in the genome of C. difficile reference strain 630, 8 within prophages (Soutourina, Toxins 2019). A careful inspection of available C. difficile phage genomes revealed even more variants of small proteins within potential type I TA that were completely missed during automatic gene annotation. Many questions remain to be addressed on these enigmatic TA modules. Future studies will help to uncover their hidden secrets. In the meantime, we are happy to share with the scientific community the improved genetic tool using the inducible expression of a toxin from type I TA for the C. difficile genome editing. We can now plan the precise manipulations of the C. difficile genome that appeared not feasible before. « Difficile » genome became now really more accessible for future investigations.

Detailed description in Communications Biology paper (Peltier et al. Communications Biology 2020) https://doi.org/10.1038/s42003-020-01448-5.

Contact : O. Soutourina olga.soutourina i2bc.paris-saclay.fr

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- Soutenance de thèse de Célia Chenebault

le 18 Décembre 2020 à 14h00

Célia Chenebault, soutiendra sa thèse intitulée « Ingénierie de cyanobactéries pour la photoproduction de terpènes (biocarburants) » le vendredi 18 décembre à 14h.

Compte tenu des contraintes sanitaires, il n’est pas encore certain qu’elle pourra se dérouler en présentiel au CNRS (1 avenue de la terrasse – Gif-sur-Yvette). Vous pourrez néanmoins y assister par visioconférence en utilisant le lien suivant : https://bbb.i2bc.paris-saclay.fr/b/che-qpk-ht7

Sa thèse s’est déroulée dans l’équipe « Biologie et Biotechnologie des Cyanobactéries »
https://www.i2bc.paris-saclay.fr/spip.php?article816

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02 December 2020 - A pathogen has been emerging ... without chasing another one

Emerging pathogens can be a threat when they affect food production or ecosystem services, by displacing resident species, and we need to understand the cause of their establishment. In this work, we studied the patterns and causes of the establishment of the bacterial plant pathogen Dickeya solani that has emerged in potato agrosystems in Europe. The Dickeya and Pectobacterium pathogens are causing blackleg disease on potato plants.
In this work, we assessed (1) the dynamics of Dickeya solani and resident pathogens (Dickeya dianthicola and Pectobacterium species) in France using epidemiologic data collected from potato fields, (2) the competitive ability of Dickeya solani against the closely-related resident Dickeya dianthicola species using experimental assays in greenhouse and (3) the natural genetic diversity of Dickeya solani using population genomics.
Over the studied decade, the Dickeya species (the sum of Dickeya solani and Dickeya dianthicola) were detected in 10% to 35% of the sampled fields exhibiting plants with blackleg disease, while the most prevalent pathogens remained the Pectobacterium species (in 65% to 90% of the symptomatic fields). Overall, the Dickeya solani establishment did not occur at the expense of Dickeya dianthicola. However, when we zoomed at the field level we observed that Dickeya dianthicola and Dickeya solani pathogens were not randomly distributed, suggesting competitive exclusion between the two pathogens. We tested this hypothesis using plant infection assays in glasshouse. Plant assays showed that Dickeya dianthicola exhibited a fitness advantage over Dickeya solani inside the lesions of potato plants, while Dickeya solani exhibited a fitness advantage over Dickeya dianthicola in diseased potato tubers. In addition, Dickeya solani exhibited a fitness advantage over Dickeya dianthicola in diseased hyacinths, which constitute a reservoir or/and primary or intermediate host of Dickeya solani. By comparing 67 Dickeya solani genomes, only 45 non-synonymous variations in coding regions were identified. One of these variations occurred at balanced frequencies between two alleles in the vfmB gene, which is involved in the poorly characterized quorum-sensing system in Dickeya pathogens. The bacterial strains carrying one vfmB allele were more aggressive on tubers, while those carrying the other vfmB allele were more competitive in potato plants. Such opposite gains across different plant organs could contribute to the maintenance of balanced frequencies of the two alleles in Dickeya solani populations.
In conclusion, this study contributes to a better understanding of the pattern and causes of the Dickeya solani emergence into potato production agrosystems, and of the reasons why Dickeya dianthicola nevertheless persisted. This inform more generally on the causes of the coexistence of related pathogens on the same hosts in ecosystems.

This work was supported by the Paris-Saclay University, CNRS and French National Research Agency (ANR) in the frame of the public-private collaborative project (PCRE) COMBICONTROL (ANR-15-CE21-0003) associating the academic laboratories I2BC (Gif-sur-Yvette- https://www.i2bc.paris-saclay.fr), MAP (Villeurbanne- https://map.insa-lyon.fr) and IEES (Paris- https://iees-paris.fr) and the private partner FN3PT (Paris- https://www.plantdepommedeterre.org). This work also involved two academic partners, ESE (Orsay- https://www.ese.universite-paris-saclay.fr) and the University of Malaya (Malaysia- https://biology.um.edu.my).

Original article : Pattern and causes of the establishment of the invasive bacterial potato pathogen Dickeya solani and of the maintenance of the resident pathogen Dickeya dianthicola
First published in Molecular Ecology : 23 Nov 2020 https://doi.org/10.1111/mec.15751

Contact : denis.faure i2bc.paris-saclay.fr

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- journées ACTINO2020 : 7 et 8 Décembre 2020- - - - - - - - - - - - - -

Un colloque intitulé les journées ACTINO2020 se déroulera en visio le Lundi 07 et le mardi 08 Décembre
Les 4 sessions proposées lors ce colloque sur les Actinobactéries seront "Génomique et évolution", "Métabolisme spécialisé et biologie de synthèse", "Interactions Actinobactéries/plantes" et "Régulation"

Cet évènement, organisé par l’équipe « Microbiologie moléculaire des Actinomycètes » de l’I2BC est gratuit, mais nécessite une inscription pour recevoir le lien de la visio. Si des personnes souhaitent assister à tout ou partie du colloque, il faut contacter Sylvie Lautru (sylvie.lautru i2bc.paris-saclay.fr) pour qu’elle vous ajoute à la liste des participants.

Programme :

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02 November 2020 - The flexizyme-based technology is a promising tool to study specialized metabolism enzymes that use aminoacyl-tRNAs as substrates

The flexizyme-based technology discovered by Suga and coll. is a powerful tool to incorporate noncanonical amino acids into peptides and proteins synthesized by cell-free systems. Flexizymes (Fx) are 45 to 47 nucleotide-long ribozymes, that catalyse the in vitro aminoacylation of tRNAs using chemically-activated amino acids or surrogates as substrates. The use of Fx allows acylation of tRNAs with a near infinite range of substrates. Moreover, as Fx bind the acceptor tRNAs via base-pairing interaction with only three nucleotides located at their conserved 3’ terminus (N73C74C75, numeration corresponding to a canonical tRNA, with N being whichever of the four nucleotides), they can aminoacylate tRNAs of any given sequences or shortened tRNA analogues (minitRNAs), such as microhelices (miHxs)[1–3] (see Figure).

The Fx-technology has recently been set up in the “EnRPB” group (Enzymology and nonRibosomal Peptide Biosynthesis, Microbiology Department, I2BC@Saclay) for studying cyclodipeptide synthases (CDPSs). CDPSs are specialized metabolism enzymes that use aminoacyl-tRNAs (AA-tRNAs) as substrates[4].
In a recent publication in Nucleic Acids Research, the EnRPB group together with the DMTS (Département Médicaments et Technologies pour la Santé, Joliot Institute), developed a production pipeline for the production of purified AA-minitRNAs. This method combines the use of Fx to aminoacylate a diversity of minitRNAs and their subsequent purifications by anion-exchange chromatography. Then, the authors were able to show that aminoacylated molecules mimicking the entire acceptor arms of tRNAs (AA-microHxs) were substrate as effective as entire AA-tRNAs, thereby demonstrating that the acceptor arms of the two substrates are the only parts of the tRNAs required for CDPS activity. The method developed in this study should greatly facilitate future investigations of the specificity of CDPSs and of other AA-tRNAs-utilising enzymes[5].

References
[1] T. Passioura, H. Suga, Top Curr Chem 2014, 344, 331–345 ; [2] H. Murakami, A. Ohta, H. Ashigai, H. Suga, Nat Methods 2006, 3, 357–359 ; [3] T. Fujino, T. Kondo, H. Suga, H. Murakami, ChemBioChem 2019, cbic.201900150 ; [4] N. Canu, M. Moutiez, P. Belin, M. Gondry, Nat. Prod. Rep. 2020, 37, 312–321 ; [5] M. Moutiez, P. Belin, M. Gondry, Chem Rev 2017, 117, 5578–5618.

Contact : Muriel Gondry

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- - - - - - — - - New PhD student in the department - - - - - - - — - - - - -

02 november 2020 - Hello, I’m ZHANG Yijie from Shanghai China, a new PhD student under the supervision of Pr Nicolas BAYAN. I obtained my Master degree of Life science at the University of Lille in 2019 and then I finished my clinical internship in Shanghai in 2020. For the following years, I will be working on the study of protein mycoloylation in Corynebacterium glutamicum. The occurrence of protein mycoloylation, its mechanism and its function are yet to be known, and I’m excited to participate in this discovery.

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26 October 2020 - Hi everyone, my name is Sara Dendene and I recently joined the team of Peter Mergaert and Denis Faure, as a new PhD student under the supervision of Benoit Alunni. I have a master degree in fundamental and applied microbiology, obtained from the University of Rennes 1, and for the next three years I’ll be working on the Sinorhizobium meliloti cell cycle regulation and its symbiosis with legume plants. I’ve been always fascinated by deciphering complex regulation networks and understanding the interaction between different organisms ; this is why I’m so enthusiastic in joining the team Mergaert-Faure.

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26 October 2020 - My name is Emanuele Biondi and I’m a CNRS scientist (section 21) since 2010 specialized in molecular genetics of bacteria with an interest in bacterial cell cycle regulation. I’ll be joining the team of Peter Mergaert and Denis Faure, where I’ll focus on the link between cell cycle and symbiosis in Sinorhizobium meliloti. I’ve been working since 2003 on phosphorylation cascades and the link between methylation of DNA and transcriptional regulation in the model system Caulobacter crescentus, which belongs to the same class as S. meliloti.

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- - - - - Habilitation à Diriger la Recherche de Christophe Regeard - - - - -

20 October 2020

Les biofilms, l’électroactivité et la corrosion de nanofilms de Fer par Shewanella oneidensis

HDR par Christophe Regeard, équipe Biologie Moléculaire des Corynebactéries et Mycobactéries le 26 Octobre 2020 à 14h dans l’auditorium du bât. 21, campus Gif-sur-Yvette

Résumé : Mes travaux de recherche en microbiologie se sont articulés autour de la bioremédiation, de la biodiversité bactérienne et phagique, des biofilms. Ces différentes approches ont pour but une meilleure compréhension des interactions entre les bactéries et leur environnement. La vie microbienne peut se développer sous une forme adhérée à une surface ou une interface et les conséquences peuvent être bénéfiques ou néfastes pour l’homme, les activités humaines, et même la planète Terre. C’est pourquoi des travaux originaux à l’interface entre la chimie et la biologie ou la physique et la biologie ont été menés. Lors de cette soutenance, les derniers résultats obtenus concernant l’étude de la corrosion de nanofilms de fer par la bactérie Shewanella oneidensis seront présentés.

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6 October 2020 - My name is Maya Long. I obtained my BTEC APA in biotechnology at Sorbonne University. I will work for a year in the MMA (Molecular Microbiology of Actinobacteria) team with Dr. Sylvie Lautru and Dr. Emmanuelle Darbon on the Streptocontrol project. I will participate in the study of the antifungal properties of a Streptomyces strain in order to develop biocontrol solutions for plant cultivation.

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1 October 2020

Hello, my name is Benjamin Hepp. I obtained a Master Degree in Microbiology at Paris Diderot University and Pasteur Institute in 2020. Now, I’m starting a PhD on hyperthermophile archaea in Jacques Oberto’s team. I am working on Thermococcales, an order of hyperthermophile archaea found in hydrothermal vents in the ocean. My aim is to decipher the action mechanism of an integrase found on a parasitic plasmid and maybe work towards some applications for this enzyme. Hyperthermophiles are very interesting ; their ability to live in an extreme environment is fascinating. I am very excited about the outcome of this work !

Hello everyone, my name is Gaëlle Lextrait. I obtained a Master degree at the Faculty of Sciences of Montpellier entitled : Interaction between Host Microorganisms and Environment. My passion for symbioses led me to do an internship in the microbiology department, in Peter Mergaert’s plant-bacteria interaction team at the Institute of Integrative Cell Biology in Gif-sur-Yvette. I am now pursuing my PhD in this same team. My research subject is the identification of the genetic determinants in the insect gut symbiont Burkholderia insecticola for specific colonization of the legume pest Riptortus pedestris. I am very excited to have an opportunity to work on this project.

My name is Romain Jouan. I obtained an engineering degree in AgroParisTech in 2020, studying forest ecology and agriculture for two years, then microbiology last year.
I am now starting my PhD in Peter Mergaert’s team on plant-bacteria interactions, under the supervision of Tania Timtchenko. I will study the interactions between the bacterium Burkholderia insecticola and multiple host species, including plants and insects (like the legume Glycine max or the stink bug Riptortus pedestris). It is a very interesting subject for me, because I was always interested in interspecific relationships.
When I do not work, I like to hike, do sports, cooking, eating, traveling... Sometimes you can even find me in the basement of Paris !
Maybe after this PhD I will be able to apply my new knowledge to other species, in a forest environment for instance.

Hello, my name is Polina and I came from Moscow (Russia). Not so long time ago I got my master’s degree in Life Sciences at Skoltech and now I am a dual PhD student at Skoltech and Paris-Saclay University. I am very excited to have an opportunity to work with Prof. Olga Soutourina and her team. I believe our collaborative project on the application of the C.difficile CRISPR-Cas system for epidemiological monitoring and infection prevention has a bright future for the world’s medicine. Wish us a productive year !

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- - - - - - - - - - Academic Life in the Department of Microbiology- - - - - - - -

30 September 2020 - Practical Course of Integrative Microbiology for the students of the M2 Fundamental Microbiology

The students of the International Master Cours in Fundamental Microbiology (Master 2 level) have started their academic year this september with a practical course of 3 weeks, hosted by the Plant-Bacteria Interactions team of the Microbiology Department and with the great help of the high-throughput sequencing, flow cytometry and microscopy facilities of the I2BC.

The 12 students coming from different scientific horizons and 7 different countries, together with their professors Olga Soutourina and Stéphanie Bury-Moné, worked together around the topic Living Together : Microbe-Host Interactions. They were divided in 3 teams and have worked on research projects in 3 different bacterium-host interaction models studied by the Plant-Bacteria Interactions team. The TA group worked on the plant tumor-forming bacterium Agrobacterium tumefaciens in interaction with one of its host plants, tomato. The MS group studied the nitrogen-fixing symbiotic association of Sinorhizobium meliloti with its host plant Medicago sativa. Finally, the gut symbiosis of the insect Riptortus pedestris with Burkholderia insecticola was the research topic of the RB group.

The leitmotiv of the 3 groups was the use of transposon-sequencing, aka Tn-seq, to identify on a genome-wide scale the bacterial functions that are important in the establishment of the interactions with their hosts. The students have learned how to make saturated transposon mutant libraries, to perform in vitro and in vivo Tn-seq screens, to prepare Illumina sequencing libraries and sequencing, to analyse high-throughput sequencing data sets in order to identify fitness genes in the bacteria, to make mutants in bacteria and phenotypically characterize these mutants in vitro and in interaction with the host plant or insect.

The cours was a great way for the students to start the new academic year with and forget the long months of the lock down, they learned a lot and obtained tons of results that will be even used by the PBI researchers for their projects.
A big thank you to the students, their professors and the members of the PBI team for their investment and enthousiasm. We had a wonderful Living Together time.

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24 September 2020 - Reprogrammed Escherichia coli for the production of dehydrogenated diketopiperazines

Natural products are an inexhaustible source of bioactive compounds for the pharmacopoeia. Among them, 2,5-diketopiperazines (2,5-DKPs) exhibit various biological activities, including antibacterial, insecticidal, anticancer and immunomodulatory. They are composed of a cyclodipeptide core resulting from the condensation of two amino acids that is tailored by diverse chemical modifications. The isolation of these compounds from the producing host is often difficult or impossible because of the uncontrolled conditions of production. The recent discovery of dedicated biosynthetic pathways has opened the way to the use of enzymes in recombinant engineering approaches to control and increase the level of production of 2,5-DKPs and biosynthesize previously undescribed 2,5-DKPs.
In a recent publication in Microbial Cell Factories, the Enzymology and Non Ribosomal Peptide Biosynthesis team (I2BC/CEA) in collaboration with the IBPS mass spectroscopy and proteomic facility (Institute of Biology Paris-Seine, Sorbonne University) and the Laboratory of Biomolecules (Sorbonne University) described the controlled production of a wide variety of dehydrogenated 2,5-DKPs by Escherichia coli. Dehydrogenation is one of the primary steps in 2,5-DKP biosynthetic pathways that plays an important role in 2,5-DKP diversification. Using synthetic biology approaches, the authors associated genes encoding bacterial cyclodipeptide synthases (CDPSs) involved in building the core of 2,5-DKPs from aminoacylated tRNAs (aa-tRNAs) and microbial cyclodipeptide oxidases (CDOs) that catalyze the dehydrogenation of the Calpha-Cbeta bonds of cyclodipeptides using molecular oxygen (Figure 1). The authors combined 18 different CDPSs and 8 different CDOs, and showed the bioproduction of 28 different mono- and di-dehydrogenated 2,5-DKPs. The site of dehydrogenation was identified unambiguously for five mono-dehydrogenated compounds, revealing novel CDO activities. Furthermore, the best combination for the bioproduction of several dehydrogenated 2,5-DKPs were identified. This work has implication in the deciphering of CDO-encoded novel biosynthetic pathways and illustrates the potential of synthetic biology for the production of new compounds in a tractable chassis by using enzyme combinations not found in nature.

Figure 1 : Schematic representation of an Escherichia coli bacterium programmed for the production of dehydrogenated 2,5-DKPs. CDPSs use aa-tRNA to produce cyclodipeptides which are then dehydrogenated by CDO. The dehydrogenated 2,5-DKPs are recovered from the culture medium.

Contact : Pascal Belin

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- - - - - - - - - - - Research topic in Frontiers in Microbiology- - - - - - - - - - -

Pr Olga Soutourina from the I2BC Microbiology department is coordinating with Dr Florence Hommais from Université Claude Bernard Lyon 1 a research topic for Frontiers in Microbiology on the "Regulatory RNAs in Bacterial Pathogens".

Regulatory RNAs play key roles in all living organisms. During an infection, bacteria reprogram the expression of their genes in response to environmental constraints in order to adapt their physiology and metabolism to host conditions. Non-coding RNAs have been recently identified as central players shaping these adaptive and pathogenic processes both in bacterium and in its host. RNAs could potentially affect all steps in the bacterial infection cycle and contribute greatly to the interactions of pathogens with their hosts, as well as other members of microbial communities, including commensal microbiota and bacteriophages.

This Research Topic will accept Original Research Articles, Reviews and Opinion pieces covering the following aspects of RNA-based regulation in pathogenic bacteria :
• The diversity of pathophysiological and metabolic processes targeted by RNAs and the diversity of the RNAs themselves (small RNAs, cis-antisense RNAs, etc)
• RNA-mediated host-pathogen crosstalk (secreted RNAs, RNA in extracellular vesicles)
• RNA-based metabolic and physiological regulations in response to stressors during infection
• RNAs within mobile genetic elements, including prophage-, pathogenicity island- and plasmid-associated RNAs
• Applications of regulatory RNAs in the development of new therapeutic strategies against pathogens

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24 June 2020 - TOWARDS A SUSTAINABLE USE OF COPPER IONS AS ANTIMICROBIALS

The use of phytosanitary products, including antimicrobials and metal ions, results in pollution of water and agricultural soil. This pollution threatens human health and the environment. In addition, the intensive application of these substances on crops contributes to the appearance of bacterial strains resistant to antibiotics or metals. Copper is widely used as an antimicrobial agent in vines, olive groves, orchards, in conventional agriculture but also in organic agriculture. This metal accumulates in soils and plants can also accumulate it in their tissue. The EU recommends lowering the copper concentrations used. It is therefore urgent to find solutions to manage agricultural production in a sustainable manner and to limit environmental and health risks.

In two studies on the toxicity of copper (Cu) and cadmium (Cd) in environmental and pathogenic bacteria (published in Microbial Biotechnology), the research team "Bacterial adaptation to environmental changes" in the microbiology department of I2BC, has shown that to survive at high concentrations of Cu or Cd, bacteria need iron import systems and a superoxide (O2.-) detoxification system. Indeed, it is shown that Cu or Cd induces the iron import system. This induction is not fortuitous, but represents a vital process in the bacterial adaptation to excess metal. The study found that iron limitation makes bacteria much more susceptible to copper poisoning, thereby significantly reducing the concentration of copper needed to kill the bacteria. Such an approach to limit copper pollution in agriculture is suggested in the first publication.

In the second study, the team showed the induction of superoxide dismutase (SOD) in all pathogenic or environmental bacteria tested, during treatment with Cu or Cd. As for the import of iron, the inactivation of this enzyme makes it possible to significantly reduce the Cu or Cd concentration necessary to eliminate the bacteria. Thus, a solution to reduce the concentration of metal used to eliminate microbes, would be to target this SOD enzyme.

Both studies suggest that metals (Cu or Cd) and superoxide target exposed 4Fe-4S clusters in proteins. Thus, the simultaneous presence of Cu and O2.- becomes lethal and the import of iron becomes necessary and vital, likely to sustain Fe-S clusters synthesis, to rebuilt Fe-S proteins. Based on these results, limiting the availability of iron or inhibiting superoxide dismutases makes bacteria much more susceptible to metal poisoning, thus making it possible to limit and lower copper concentrations towards a sustainable and respectful management of agricultural land in the context of the use of metal ions as antimicrobials.

Contact : Soufian Ouchane

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25 May 2020 - FUNCTION OF ANTIBIOTICS FOR THE PRODUCING BACTERIA ?

Most of the antibiotics in current use are produced by Streptomyces species, Gram + filamentous bacteria living in the superficial layers of the soil. The team " Energetic Metabolism of Streptomyces" (MES) of the "Microbiology" department of I2BC tries to determine in which context these bioactive molecules are being produced and what are their functions for the producing bacteria.
Their studies demonstrated that phosphate limitation is a major trigger of antibiotics biosynthesis (1). Under such conditions of energy stress (ATP deficit), various processes are being triggered in order to restore the energetic balance of the cell. These include the up-regualtion of the expression of enzymes generating reduced co-factors (NADH) including those belonging to the TriCarboxylic Acid cycle (TCA) as the re-oxidation of NADH by the respiratory chain generates ATP. Such activation of the TCA cycle and thus of "oxidative phosphorylation" requires intensive fueling of the TCA by acetyl-CoA. Consequently, high antibiotic producing strains usually contain little or no storage lipids of the TriAcylGlycerol (TAG) family since the synthesis of these neutral lipids also requires acetyl-CoA (2). However, a strong activation of "oxidative phosphorylation" that results into high ATP generation cannot proceed in a situation of phosphate scarcity. Such situation would cause a dysfunction of the respiratory chain leading to the generation of reactive oxygen and nitrogen species (ROS and NOS) that are thought to constitute signals triggering antibiotics biosynthesis. Some antibiotics (Type I) would create damage to the membrane resulting into lysis of a fraction of the population to provide nutriments and especially phosphate to the surviving population (3). Other antibiotics (Type II) would reduce the electron flow of the respiratory chain via their ability to capture electrons in order to adjust and reduce ATP generation to low phosphate availability (2, 3). Doing so, they would also combat oxidative stress (1, 3). Finally, the last type of antibiotic (Type III) would inhibit various ATP consuming anabolic processes (cell wall/membrane, proteins, nucleic acids synthesis) to save ATP in conditions of phosphate scarcity (3). These three types of antibiotics target different cellular processes but they would all be involved in the regulation of the energetic metabolism of the bacterium in conditions of phosphate limitation / scarcity (3).
The endogenous roles proposed for the antibiotics and their traditionally proposed exogenous role of weapons conferring competitiveness in their ecological niche constitute simply the two sides of the same coin (3). Indeed these molecules are similarly toxic for their producer and for micro-organisms of the environnement, but the very strict temporal control of their biosynthesis and the induction of resistance determinants limit their toxicity to a very short period in the producer. In contrast, environmental microorganisms are likely to be sensitive to these harmful molecules, since they do not possess similar resistance mechanisms as the producing strains do (3).

(1) Millan-Oropeza et al., 2020 Scientific Reports
(2) Esnault et al., 2017 Scientific Reports
(3) Virolle 2020
see Scoop.It Life Sciences Université Paris-Saclay for a french version of this summary

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Des membres du Département de Microbiologie engagés dans la lutte contre le Covid-19

La très grande majorité des membres du département sont confinés chez eux et poursuivent leurs activités de recherche et d’enseignement par télétravail.
L’équipe Endotoxines, Structures et Réponses de l’Hôte est engagée en première ligne dans la lutte contre le Covid-19. Le Pr. Pierre Tissières, chef du service réanimation pédiatrique et néonatale à l’Hôpital Bicêtre, le Pr. Florence Doucet-Populaire et le Dr. Nadège Bourgeois-Nicolaos, du service Bactériologie Hygiène à l’Hôpital-Béclère, sont en première ligne dans cette bataille sanitaire sans précédent. Ils soignent les malades en service de soins intensifs et sont impliqués dans le dépistage du coronavirus.

Merci pour leur implication et leur dévouement.

Leur message à nous tous : respectez l’isolement car c’est une maladie vraiment très contagieuse et vraiment sévère, sans commune mesure avec la grippe saisonnière.

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- - - - New publication of the Department in Molecular Microbiology - - - -

9 April 2020 - The team of Nicolas Bayan published the paper entitled "The C-terminal domain of Corynebacterium glutamicum mycoloyltransferase A is composed of five repeated motifs involved in cell wall binding and stability" in Molecular Microbiology. Dietrich et al. Mol. Microbiol. 2020 Feb 19. doi : 10.1111/mmi.14492.

The genomes of Mycobacteria and related species contain several genes encoding mycoloyltransferases that are specific cell envelope enzymes essential for the biogenesis of the outer membrane. We determined the crystal structure of the major mycoloyltransferase MytA of Corynebacterium glutamicum and found that its C-terminal domain forms a stalk composed of five repeated LGFP motifs (4-stranded beta-fold) that interact specifically with the cell wall peptidoglycan-arabinogalactan polymer and contribute to the overall stability of the cell envelope. This is the first characterization of a specific carbohydrate binding motif identified in cell wall proteins of M. tuberculosis and related bacteria.

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- - - - - - - - New publication of the Department in ISME Journal - - - - - - - -

1 April 2020 - Burkholderia insecticola triggers midgut closure in the bean bug Riptortus pedestris to prevent secondary bacterial infections of midgut crypts

Symbioses with beneficial microbes are essential for the normal growth of organisms. How organisms maintain these specific mutualisms is a fundamental question. In many symbioses, hosts acquire their specific symbionts from the environment every new generation, requiring sophisticated mechanisms to winnow out the desired bacteria from the large diversity of environmental bacteria. The symbiosis between the insect Riptortus pedestris and its gut symbiont Burkholderia insecticola is one of the model systems that is studied by researchers of the Microbiology Department of I2BC to understand how specificity in mutualistic interactions is maintained.

This insect houses its symbiont in a specific region of the gut composed of crypts that are fully occupied with millions of these bacteria. It uses different strategies to make sure that only the right symbiont occupies these crypts. One of them is a very strict check at the entrance of the crypt region, allowing only those bacteria with the right “ticket” to pass the gate. A second mechanism is based on competition between bacteria in the crypts leading to the efficient elimination of any contaminating bacteria that managed anyhow to enter despite the control at the entrance. In a new study published this March in the ISME Journal, the I2BC researchers, in collaboration with a Japanese team, have identified an additional feature enabling the insect to keep exclusivity for the symbiont in the crypts. Spatiotemporal microscopic observations of the infection process with bacteria labelled with a fluorescent protein revealed that after the initial passage of symbionts through the gate of the crypt region, it closes very rapidly and permanently, blocking any potential subsequent entry of unwanted microbes. This work thus expands the understanding of how animals sustain specific gut symbiosis.


The symbiotic crypt region of the insect intestine is occupied with a “red” symbiont. The “green” symbiont which was administered a few hours after the “red” one can not enter the crypt region because the gate was closed immediately after the entry of the red strain.

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- - - - - - New publication of the Department in Scientific Reports - - - - - -

Natural products are an inexhaustible source of bioactive compounds for the pharmacopoeia. Among them, prenylated indole diketopiperazines exhibit various biological activities, including antibacterial, insecticidal, anticancer and immunomodulatory. They derive from the condensation of tryptophan with another amino acid and are produced mainly by filamentous fungi. However, the isolation of these compounds from the producing host is often difficult or impossible because of the uncontrolled conditions of production.

In a recent publication in Scientific Reports, the team Enzymology and Non Ribosomal Peptide Biosynthesis (I2BC/CEA) in collaboration with the SIMOPRO (CEA) and the Laboratory of Biomolecules (Sorbonne University) described the controlled production of prenylated indole diketopiperazines by the bacterium Escherichia coli. By using synthetic biology approaches, the authors associated genes encoding bacterial cyclodipeptide synthases (CDPSs) involved in building the core of the molecules and fungal prenyl transferases (PTs) that catalyze the anchoring of a prenyl group to the indole moiety of the tryptophan-containing cyclodipeptides. In addition, the authors showed that the production of prenylated indole diketopiperazines was increased by the expression in bacteria of seven other genes encoding a recombinant pathway for dimethylallyl diphosphate (DMAPP), a PT substrate essential for the transfer of the prenyl group (Figure 1). Of the 11 CDPS/PT tested combinations, seven were found to be effective for the production of prenylated indole diketopiperazines that were purified and characterized by NMR spectroscopy. This work illustrates the potential of synthetic biology for the production of new bioactive compounds in a tractable chassis by using enzyme combinations not found in nature.

Figure 1 : Schematic representation of an Escherichia coli bacterium programmed for the production of prenylated indole diketopiperazines. CDPSs use aminoacylated tRNAs (aa-tRNA) to produce cyclodipeptides which are then prenylated by PTs. This latter reaction is enhanced when the intracellular pool of DMAPP (shown in orange) is increased. The prenylated indole diketopiperazines are recovered from the culture medium. Glu-3P, glucose-3-phosphate.
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- - - - - - - - - - - - - - - New member of the department - - - - - - - - - - - - - - - -

We are pleased to welcome Johann Peltier who has just been recruited as an Assistant Professor at Paris-Sud University and will join the “Regulatory RNAs in Clostridia” team in September 2019.
Congratulations to Johann for this performance !

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- - - - - - - - - - - - - - - New member of the department - - - - - - - - - - - - - - - -

Congratulations to Emma Piattelli for getting the PhD fellowship to start her PhD thesis in October 2019 in the « Regulatory RNAs in Clostridia” team under the supervision of Pr Olga Soutourina. Welcome to Emma and good luck for her work on the role of non-coding RNAs in the pathogenesis of Clostridium difficile.

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- - - - - - - - - - I2BC Microbiology Department Meeting 2019 - - - - - - - - - - -



The yearly I2BC Microbiology Department Meeting will be held on Friday June 7th in the Auditiorium of Bât. 21 in Gif-sur-Yvette (CNRS campus).

The theme of this year is “Microbiology and Health” with the following four sessions :

1) Biotechnology and Health
2) Horizontal Gene Transfer/Antibiotic Resistance/Gut Microbiota
3) Biology of Pathogens
4) Innate Immunity

Download the detailed program :

For inscription (free !), click here.
Please indicate your participation to the morning session, lunch (offered by the Department) and afternoon session. You also have the possibility to present a Poster. Please send us by e-mail to Peter Mergaert or Nicolas Mirouze your Poster Abstract. Be sure to use your e-mail address in the doodle so that we can send you updates of the program.

We are looking forward to see you in the meeting,

The Microbiology Department


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- - - - - - - - - - - - - - - - - - - - - - - - Meeting - - - - - - - - - - - - - - - - - - - - - - -


MICROBES DAY.........still time to register !!!!!!! !

For the first time, we organized an inter Paris-Saclay laboratories meeting around Microbiology. The Paris-Saclay MICROBES day, held on Wednesday March 27th 2019 at Gif-sur-Yvette, will showcase the diversity of Microbiology research performed at Paris-Saclay University. This event gathers a community of experts exploring the multiple facets of Microbiology (bacteria, archaea, microbial eukaryotes & viruses) across all scales : from molecules to genes, genomes, cells, populations, communities, and from basic sciences to applied innovations in microbial and molecular engineering and from environmental to human health.

Session 1 : Microbial ecology and evolution

Session 2 : From molecules to microbial cells

Session 3 : Molecular and microbial engineering

Session 4 : Host-microbes interactions and health microbiology

more info : https://microbes-day.sciencesconf.org/

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- - - - - - New publication of the Department in New Phytologist - - - - - - -

17 January 2019 - The biotrophic pathogen Agrobacterium tumefaciens genetically transforms plants and thereby induces the formation of plant tumors which constitute a specific niche for the pathogen. In a paper recently published on-line in The New Phytologist (The biotroph Agrobacterium tumefaciens thrives in tumors by exploiting a wide spectrum of plant host metabolites Almudena Gonzalez‐Mula, Joy Lachat ,Léo Mathias Delphine Naquin Florian Lamouche Peter Mergaert Denis Faure), Denis Faure and his colleagues described how the pathogen mobilizes its central metabolism for exploiting a wide diversity of nutrient resources present in the tumor.

A combination of omics revealed some metabolic pathways involved in the plant host exploitation by the biotroph Agrobacterium tumefaciens.

The diversity and abundance of plant metabolites in plant tumors was characterized by metabolomics, and then transposon-sequencing and transcriptomics were used for identifying the Agrobacterium key-genes involved in the exploitation of some metabolites as a source of nutrients. Finally, reverse genetics allowed to verify the role of these genes in aggressiveness and fitness of Agrobacterium when it colonizes the plant tumors. This work highlights how a biotroph mobilizes its central metabolism for exploiting a wide diversity of resources in plant host. It further shows the complementarity of functional genome-wide scans by transcriptomics and transposon-sequencing to decipher the lifestyle of a plant pathogen.

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- - - - - - - - Master of Fundamental Microbiology of Paris Saclay - - - - - - -


Our 2018-2019 class propose a digest of recent articles in Microbiology


1- Nicolas Alexandre : Insights in Bdellovibrio bacteriovorus predation

2- Emile Auria : Bacteriophages cooperation

3- Kimberley Casado : Cohabitation with the enemy !

4- Nicolas Ducrot : Co-production of therapeutic drugs by yeast

5- Antony Goudin : Giant viruses

6- Virgile Gueneau : Pathogen elimination by probiotic Bacillus

7- Hugo Guerin : Electrical communication in bacterial communities

8- Gaetan Pavard : Control of dormancy in Cyanobacteria

9- Emma Piattelli : Engineering bacteria to eradicate Malaria

10- Marius Poulain : Symbiosis in marine sponges

11- Gabriella Sarango : Bacteria-electronic devices for health

12- Louise Sibleyras : Bacterial Prions

13- Léa Swistak : OMVs and toxin delivery

- - - - - - - - - - - Have a nice reading and ....... Happy 2019 !!! - - - - - - - - - - -


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- - - - New publication of the Department in Nature Communications - - -

30 November 2018 - In a paper published today online in Nature Communications, the Mirouze team report that wall teichoic acids (WTAs), cell wall-anchored anionic glycopolymers associated to numerous critical functions in Gram-positive bacteria, are involved in this initial step of transformation. Using a combination of cell wall-targeting antibiotics and fluorescence microscopy, the team show that competence-specific WTAs are produced and specifically localized in the competent cells to mediate DNA binding at the proximity of the transformation apparatus. On the basis of their results and previous knowledge in the field, they propose a new model for DNA binding and transport during genetic transformation in B. subtilis.

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- - - - - - - - - The International Balzan Prize for Eva Kondorosi - - - - - - - - -

23 November 2018 - Today, Eva Kondorosi, former member of the Plant-Bacteria Interactions group of the department, received out of the hands of the President of the Italian Republic the Balzan Prize for Chemical Ecology.
Eva made the largest part of her carreer as a CNRS researcher, first in the ISV and then in the I2BC. Presently she is in the Biological Research Center of the Hungarian Academy of Sciences in Szeged, Hungary.
She received the award for her lifelong work on understanding the symbiosis between legume plants and soil bacteria known as rhizobia. Eva Kondorosi is renowned for her work on dissecting this interaction ; identifying the Rhizobium nodulation genes whose products, the Nod factors, trigger nodule development and bacterial infection in the host plant and discovering hundreds of nodule cysteine-rich plant peptides which are important signaling molecules and effectors of the differentiation of endosymbionts.


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- - - - - - - - - - - - - - - - - - - Fête de la science 2018 - - - - - - - - - - - - - - - - - - -

15 October 2018

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- - - Adam Kondorosi Academia Europaea Award for Peter Mergaert - - -

30 August 2018 - Peter Mergaert receives this year’s Adam Kondorosi Academia Europaea Award for Early Career Investigators for his work on bacterial differentiation during the Rhizobium-legume symbiosis. He received the prize during the 13th European Nitrogen Fixation Conference in Stockholm this august.

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