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Publications Département Microbiologie


  • G. Bourgeois, J. Seguin, M. Babin, P. Belin, M. Moutiez, Y. Mechulam, M. Gondry, et E. Schmitt, « Structural basis for partition of the cyclodipeptide synthases into two subfamilies », Journal of Structural Biology, 2018.

  • N. Canu, P. Belin, R. Thai, I. Correia, O. Lequin, J. Seguin, M. Moutiez, et M. Gondry, « Incorporation of Non-canonical Amino Acids into 2,5-Diketopiperazines by Cyclodipeptide Synthases », Angewandte Chemie (International Ed. in English), vol. 57, nᵒ 12, p. 3118-3122, mars 2018.
    Résumé : The manipulation of natural product biosynthetic pathways is a powerful means of expanding the chemical diversity of bioactive molecules. 2,5-diketopiperazines (2,5-DKPs) have been widely developed by medicinal chemists, but their biological production is yet to be exploited. We introduce an in vivo method for incorporating non-canonical amino acids (ncAAs) into 2,5-DKPs using cyclodipeptide synthases (CDPSs), the enzymes responsible for scaffold assembly in many 2,5-DKP biosynthetic pathways. CDPSs use aminoacyl-tRNAs as substrates. We exploited the natural ability of aminoacyl-tRNA synthetases to load ncAAs onto tRNAs. We found 26 ncAAs to be usable as substrates by CDPSs, leading to the enzymatic production of approximately 200 non-canonical cyclodipeptides. CDPSs constitute an efficient enzymatic tool for the synthesis of highly diverse 2,5-DKPs. Such diversity could be further expanded, for example, by using various cyclodipeptide-tailoring enzymes found in 2,5-DKP biosynthetic pathways.
    Mots-clés : biocatalysis, BIOSYN, biosynthesis, Cyclodipeptide synthases, cyclodipeptides, Diketopiperazines, MICROBIO, Natural product engineering, Non-canonical amino acid.

  • R. Catchpole, A. Gorlas, J. Oberto, et P. Forterre, « A series of new E. coli-Thermococcus shuttle vectors compatible with previously existing vectors », Extremophiles: Life Under Extreme Conditions, mars 2018.
    Résumé : Hyperthermophilic microorganisms are an important asset in the toolkits of biotechnologists, biochemists and evolutionary biologists. The anaerobic archaeon, Thermococcus kodakarensis, has become one of the most useful hyperthermophilic model species, not least due to its natural competence and genetic tractability. Despite this, the range of genetic tools available for T. kodakarensis remains limited. Using sequencing and phylogenetic analyses, we determined that the rolling-circle replication origin of the cryptic mini-plasmid pTP2 from T. prieurii is suitable for plasmid replication in T. kodakarensis. Based on this replication origin, we present a novel series of replicative E. coli-T. kodakarensis shuttle vectors. These shuttle vectors have been constructed with three different selectable markers, allowing selection in a range of T. kodakarensis backgrounds. Moreover, these pTP2-derived plasmids are compatible with the single-existing E. coli-T. kodakarensis shuttle vector, pLC70. We show that both pTP2-derived and pLC70-derived plasmids replicate faithfully while cohabitating in T. kodakarensis cells. These plasmids open the door for new areas of research in plasmid segregation, DNA replication and gene expression.
    Mots-clés : Archaea, ARCHEE, Cloning, Gene cloning and expression, Genetics of extremophiles, Hyperthermophiles, MICROBIO, Molecular biology, Molecular biology of archaea.

  • F. Coll, J. Phelan, G. A. Hill-Cawthorne, M. B. Nair, K. Mallard, S. Ali, A. M. Abdallah, S. Alghamdi, M. Alsomali, A. O. Ahmed, S. Portelli, Y. Oppong, A. Alves, T. B. Bessa, S. Campino, M. Caws, A. Chatterjee, A. C. Crampin, K. Dheda, N. Furnham, J. R. Glynn, L. Grandjean, D. Minh Ha, R. Hasan, Z. Hasan, M. L. Hibberd, M. Joloba, E. C. Jones-López, T. Matsumoto, A. Miranda, D. J. Moore, N. Mocillo, S. Panaiotov, J. Parkhill, C. Penha, J. Perdigão, I. Portugal, Z. Rchiad, J. Robledo, P. Sheen, N. T. Shesha, F. A. Sirgel, C. Sola, E. Oliveira Sousa, E. M. Streicher, P. V. Helden, M. Viveiros, R. M. Warren, R. McNerney, A. Pain, et T. G. Clark, « Genome-wide analysis of multi- and extensively drug-resistant Mycobacterium tuberculosis », Nature Genetics, janv. 2018.

  • D. Couvin, A. Bernheim, C. Toffano-Nioche, M. Touchon, J. Michalik, B. Néron, E. P. C Rocha, G. Vergnaud, D. Gautheret, et C. Pourcel, « CRISPRCasFinder, an update of CRISRFinder, includes a portable version, enhanced performance and integrates search for Cas proteins », Nucleic Acids Research, mai 2018.
    Résumé : CRISPR (clustered regularly interspaced short palindromic repeats) arrays and their associated (Cas) proteins confer bacteria and archaea adaptive immunity against exogenous mobile genetic elements, such as phages or plasmids. CRISPRCasFinder allows the identification of both CRISPR arrays and Cas proteins. The program includes: (i) an improved CRISPR array detection tool facilitating expert validation based on a rating system, (ii) prediction of CRISPR orientation and (iii) a Cas protein detection and typing tool updated to match the latest classification scheme of these systems. CRISPRCasFinder can either be used online or as a standalone tool compatible with Linux operating system. All third-party software packages employed by the program are freely available. CRISPRCasFinder is available at
    Mots-clés : BDG, LGBMB, MICROBIO, SSFA.

  • M. Crüsemann, R. Reher, I. Schamari, A. O. Brachmann, T. Ohbayashi, M. Kuschak, D. Malfacini, A. Seidinger, M. Pinto-Carbó, R. Richarz, T. Reuter, S. Kehraus, A. Hallab, M. Attwood, H. B. Schiöth, P. Mergaert, Y. Kikuchi, T. F. Schäberle, E. Kostenis, D. Wenzel, C. E. Müller, J. Piel, A. Carlier, L. Eberl, et G. M. König, « Heterologous Expression, Biosynthetic Studies, and Ecological Function of the Selective Gq-Signaling Inhibitor FR900359 », Angewandte Chemie (International Ed. in English), vol. 57, nᵒ 3, p. 836-840, janv. 2018.
    Résumé : The cyclic depsipeptide FR900359 (FR), isolated from the tropical plant Ardisia crenata, is a strong and selective inhibitor of Gq proteins, making it an indispensable pharmacological tool to study Gq-related processes, as well as a promising drug candidate. Gq inhibition is a novel mode of action for defense chemicals and crucial for the ecological function of FR, as shown by in vivo experiments in mice, its affinity to insect Gq proteins, and insect toxicity studies. The uncultured endosymbiont of A. crenata was sequenced, revealing the FR nonribosomal peptide synthetase (frs) gene cluster. We here provide a detailed model of FR biosynthesis, supported by in vitro enzymatic and bioinformatic studies, and the novel analogue AC-1, which demonstrates the flexibility of the FR starter condensation domains. Finally, expression of the frs genes in E. coli led to heterologous FR production in a cultivable, bacterial host for the first time.
    Mots-clés : biosynthesis, FR900359, G proteins, G proteins, Heterologous expression, MICROBIO, natural products, PBI.

  • V. Da Cunha, M. Gaia, A. Nasir, et P. Forterre, « Asgard archaea do not close the debate about the universal tree of life topology », PLOS Genetics, vol. 14, nᵒ 3, p. e1007215, mars 2018.

  • Y. Dessaux et D. Faure, « Niche Construction and Exploitation by Agrobacterium: How to Survive and Face Competition in Soil and Plant Habitats », Berlin, Heidelberg: Springer Berlin Heidelberg, 2018.

  • Y. Dessaux et D. Faure, « Quorum Sensing and Quorum Quenching in Agrobacterium: A "Go/No Go System"? », Genes, vol. 9, nᵒ 4, avr. 2018.
    Résumé : The pathogen Agrobacterium induces gall formation on a wide range of dicotyledonous plants. In this bacteria, most pathogenicity determinants are borne on the tumour inducing (Ti) plasmid. The conjugative transfer of this plasmid between agrobacteria is regulated by quorum sensing (QS). However, processes involved in the disturbance of QS also occur in this bacteria under the molecular form of a protein, TraM, inhibiting the sensing of the QS signals, and two lactonases BlcC (AttM) and AiiB that degrade the acylhomoserine lactone (AHL) QS signal. In the model Agrobacteriumfabrum strain C58, several data, once integrated, strongly suggest that the QS regulation may not be reacting only to cell concentration. Rather, these QS elements in association with the quorum quenching (QQ) activities may constitute an integrated and complex “go/no go system” that finely controls the biologically costly transfer of the Ti plasmid in response to multiple environmental cues. This decision mechanism permits the bacteria to sense whether it is in a gall or not, in a living or decaying tumor, in stressed plant tissues, etc. In this scheme, the role of the lactonases selected and maintained in the course of Ti plasmid and agrobacterial evolution appears to be pivotal.
    Mots-clés : (p)ppGpp, Agrobacterium, GABA, lactonase, MICROBIO, PBI, proline, quorum quenching, quorum sensing, Ti plasmid.

  • A. Durand, M. - L. Bourbon, A. - S. Steunou, B. Khalfaoui-Hassani, C. Legrand, A. Guitton, C. Astier, et S. Ouchane, « Biogenesis of the bacterial cbb3 cytochrome c oxidase: Active subcomplexes support a sequential assembly model », The Journal of Biological Chemistry, vol. 293, nᵒ 3, p. 808-818, janv. 2018.
    Résumé : The cbb3 oxidase has a high affinity for oxygen and is required for growth of bacteria, including pathogens, in oxygen-limited environments. However, the assembly of this oxidase is poorly understood. Most cbb3 are composed of four subunits: the catalytic CcoN subunit, the two cytochrome c subunits (CcoO and CcoP) involved in electron transfer, and the small CcoQ subunit with an unclear function. Here, we address the role of these four subunits in cbb3 biogenesis in the purple bacterium Rubrivivax gelatinosus Analyses of membrane proteins from different mutants revealed the presence of active CcoNQO and CcoNO subcomplexes and also showed that the CcoP subunit is not essential for their assembly. However, CcoP was required for the oxygen reduction activity in the absence of CcoQ. We also found that CcoQ is dispensable for forming an active CcoNOP subcomplex in membranes. CcoNOP exhibited oxygen reductase activity, indicating that the cofactors (hemes b and copper for CcoN and cytochromes c for CcoO and CcoP) were present within the subunits. Finally, we discovered the presence of a CcoNQ subcomplex and showed that CcoN is the required anchor for the assembly of the full CcoNQOP complex. On the basis of these findings, we propose a sequential assembly model in which the CcoQ subunit is required for the early maturation step: CcoQ first associates with CcoN before the CcoNQ-CcoO interaction. CcoP associates to CcoNQO subcomplex in the late maturation step, and once the CcoNQOP complex is fully formed, CcoQ is released for degradation by the FtsH protease. This model could be conserved in other bacteria, including the pathogenic bacteria lacking the assembly factor CcoH as in R. gelatinosus.
    Mots-clés : BACADA, bacteria, cbb3 cytochrome c oxidase biogenesis, cytochrome oxidase, Membrane protein, MICROBIO.

  • M. El Ghachi, N. Howe, C. - Y. Huang, V. Olieric, R. Warshamanage, T. Touzé, D. Weichert, P. J. Stansfeld, M. Wang, F. Kerff, et M. Caffrey, « Crystal structure of undecaprenyl-pyrophosphate phosphatase and its role in peptidoglycan biosynthesis », Nature Communications, vol. 9, nᵒ 1, 2018.

  • D. Faure, J. - C. Simon, et T. Heulin, « Holobiont: a conceptual framework to explore the eco-evolutionary and functional implications of host-microbiota interactions in all ecosystems », The New Phytologist, vol. 218, nᵒ 4, p. 1321-1324, juin 2018.
    Mots-clés : evolution, holobiont, hologenome, MICROBIO, microbiome, microbiota, PBI, plant-microbiota interactions.

  • M. J. Fer, L. L. Corre, N. Pietrancosta, N. Evrard-Todeschi, S. Olatunji, A. Bouhss, S. Calvet-Vitale, et C. Gravier-Pelletier, « Bacterial Transferase MraY, a Source of Inspiration towards New Antibiotics », Current Medicinal Chemistry, vol. 25, mars 2018.

  • M. Gondry, I. B. Jacques, R. Thai, M. Babin, N. Canu, J. Seguin, P. Belin, J. - L. Pernodet, et M. Moutiez, « A Comprehensive Overview of the Cyclodipeptide Synthase Family Enriched with the Characterization of 32 New Enzymes », Frontiers in Microbiology, vol. 9, p. 46, 2018.
    Résumé : Cyclodipeptide synthases (CDPSs) use as substrates two amino acids activated as aminoacyl-tRNAs to synthesize cyclodipeptides in secondary metabolites biosynthetic pathways. Since the first description of a CDPS in 2002, the number of putative CDPSs in databases has increased exponentially, reaching around 800 in June 2017. They are likely to be involved in numerous biosynthetic pathways but the diversity of their products is still under-explored. Here, we describe the activity of 32 new CDPSs, bringing the number of experimentally characterized CDPSs to about 100. We detect 16 new cyclodipeptides, one of which containing an arginine which has never been observed previously. This brings to 75 the number of cyclodipeptides formed by CDPSs out of the possible 210 natural ones. We also identify several consensus sequences related to the synthesis of a specific cyclodipeptide, improving the predictive model of CDPS specificity. The improved prediction method enables to propose the main product synthesized for about 80% of the CDPS sequences available in databases and opens the way for the deciphering of CDPS-dependent pathways. Analysis of phylum distribution and predicted activity for all CDPSs identified in databases shows that the experimentally characterized set is representative of the whole family. Our work also demonstrates that some cyclodipeptides, precursors of diketopiperazines with interesting pharmacological properties and previously described as being synthesized by fungal non-ribosomal peptide synthetases, can also be produced by CDPSs in bacteria.
    Mots-clés : ACTINO, activity prediction, BIOSYN, Biosynthetic Pathways, cyclodipeptide MS/MS, cyclodipeptide synthase, diketopiperazine, MICROBIO, Secondary metabolites, tRNA-dependent enzymes.

  • A. González-Mula, J. Lang, C. Grandclément, D. Naquin, M. Ahmar, L. Soulère, Y. Queneau, Y. Dessaux, et D. Faure, « Lifestyle of the biotroph Agrobacterium tumefaciens in the ecological niche constructed on its host plant », The New Phytologist, avr. 2018.
    Résumé : Agrobacterium tumefaciens constructs an ecological niche in its host plant by transferring the T-DNA from its Ti plasmid into the host genome and by diverting the host metabolism. We combined transcriptomics and genetics for understanding the A. tumefaciens lifestyle when it colonizes Arabidopsis thaliana tumors. Transcriptomics highlighted: a transition from a motile to sessile behavior that mobilizes some master regulators (Hfq, CtrA, DivK and PleD); a remodeling of some cell surface components (O-antigen, succinoglucan, curdlan, att genes, putative fasciclin) and functions associated with plant defense (Ef-Tu and flagellin pathogen-associated molecular pattern-response and glycerol-3-phosphate and nitric oxide signaling); and an exploitation of a wide variety of host resources, including opines, amino acids, sugars, organic acids, phosphate, phosphorylated compounds, and iron. In addition, construction of transgenic A. thaliana lines expressing a lactonase enzyme showed that Ti plasmid transfer could escape host-mediated quorum-quenching. Finally, construction of knock-out mutants in A. tumefaciens showed that expression of some At plasmid genes seemed more costly than the selective advantage they would have conferred in tumor colonization. We provide the first overview of A. tumefaciens lifestyle in a plant tumor and reveal novel signaling and trophic interplays for investigating host-pathogen interactions.
    Mots-clés : Agrobacterium, Arabidopsis, horizontal transfer, MICROBIO, NGS, niche exploitation, opine, PBI, PF, plasmid, quorum-sensing, tumor.

  • B. Gourion et B. Alunni, « Strain-Specific Symbiotic Genes: A New Level of Control in the Intracellular Accommodation of Rhizobia Within Legume Nodule Cells », Molecular plant-microbe interactions: MPMI, vol. 31, nᵒ 3, p. 287-288, mars 2018.
    Résumé : This is a short commentary on the article by Wang et al. published in MPMI Vol. 31, No. 2, pages 240-248.
    Mots-clés : MICROBIO, PBI.

  • B. Gronenborn, J. W. Randles, D. Knierim, Q. Barrière, H. J. Vetten, N. Warthmann, D. Cornu, T. Sileye, S. Winter, et T. Timchenko, « Analysis of DNAs associated with coconut foliar decay disease implicates a unique single-stranded DNA virus representing a new taxon », Scientific Reports, vol. 8, nᵒ 1, 2018.
    Mots-clés : MICROBIO, PBI, PF, SICAPS.

  • M. Hrast, M. Jukič, D. Patin, J. Tod, C. G. Dowson, D. I. Roper, H. Barreteau, et S. Gobec, « In silico identification, synthesis and biological evaluation of novel tetrazole inhibitors of MurB », Chemical Biology & Drug Design, vol. 91, nᵒ 6, p. 1101-1112, 2018.

  • Y. Ishino, M. Krupovic, et P. Forterre, « History of CRISPR-Cas from Encounter with a Mysterious Repeated Sequence to Genome Editing Technology », Journal of Bacteriology, vol. 200, nᵒ 7, avr. 2018.
    Résumé : Clustered regularly interspaced short palindromic repeat (CRISPR)-Cas systems are well-known acquired immunity systems that are widespread in archaea and bacteria. The RNA-guided nucleases from CRISPR-Cas systems are currently regarded as the most reliable tools for genome editing and engineering. The first hint of their existence came in 1987, when an unusual repetitive DNA sequence, which subsequently was defined as a CRISPR, was discovered in theEscherichia coligenome during an analysis of genes involved in phosphate metabolism. Similar sequence patterns were then reported in a range of other bacteria as well as in halophilic archaea, suggesting an important role for such evolutionarily conserved clusters of repeated sequences. A critical step toward functional characterization of the CRISPR-Cas systems was the recognition of a link between CRISPRs and the associated Cas proteins, which were initially hypothesized to be involved in DNA repair in hyperthermophilic archaea. Comparative genomics, structural biology, and advanced biochemistry could then work hand in hand, not only culminating in the explosion of genome editing tools based on CRISPR-Cas9 and other class II CRISPR-Cas systems but also providing insights into the origin and evolution of this system from mobile genetic elements denoted casposons. To celebrate the 30th anniversary of the discovery of CRISPR, this minireview briefly discusses the fascinating history of CRISPR-Cas systems, from the original observation of an enigmatic sequence inE. colito genome editing in humans.
    Mots-clés : archaea, ARCHEE, casposon, genome editing, MICROBIO, repeated sequence.

  • S. Khayi, P. Blin, T. M. Chong, K. - G. Chan, et D. Faure, « Complete Chromosome and Plasmid Sequences of Two Plant Pathogens, Dickeya solani Strains D s0432-1 and PPO 9019 », Genome Announcements, vol. 6, nᵒ 17, avr. 2018.
    Résumé : Dickeya solani species are emerging bacterial pathogens of Solanum tuberosum Here, we announce the complete genome sequences of two strains, Dickeya solani D s0432-1 and PPO 9019. Strain PPO 9019 represents the first described member of the genus Dickeya with an extrachromosomal genetic element.
    Mots-clés : MICROBIO, PBI.

  • N. Kieffer, P. Nordmann, A. M. Moreno, L. Z. Moreno, R. Chaby, A. Breton, P. Tissières, et L. Poirel, « Genetic and functional characterization of an MCR-3-like producing Escherichia coli recovered from swine, Brazil », Antimicrobial Agents and Chemotherapy, avr. 2018.
    Résumé : A collection of 126 pigs were screened for carriage of colistin-resistant Enterobacteriaceae in a farm in Minas Gerais, Brazil. Out of this collection, eigth colistin-resistant Escherichia coli isolates were recovered, including one from Minas Gerais State, producing a new MCR-3 variant (MCR-3.12). Analysis of the lipopolysaccharide revealed that MCR-3.12 had a similar function as MCR-1 and MCR-2 by adding a phosphoethanolamine group to the lipid A. Genetic analysis showed that the mcr-3.12 gene was carried by an IncA/C2 plasmid and was embedded in an original genetic environment. This study reports the occurrence of the MCR-3-like determinant in South America and firstly demonstrates the functionality of this group of enzymes as a phosphoethanolamine transferase.
    Mots-clés : ESHR, MICROBIO.

  • L. Latino et C. Pourcel, « Recovery and Characterization of Bacteria Resisting Infection by Lytic Bacteriophage », Methods in Molecular Biology (Clifton, N.J.), vol. 1693, p. 85-98, 2018.
    Résumé : Bacteria and bacteriophages coexist and coevolve, bacteriophages being obligatory predators exerting an evolutionary pressure on their prey. Mechanisms in action vary depending on the bacterial genomic content and on the regulation of the bacteriophage cycle. To assess the multiplicity of bacterial genes involved in resistance as well as the changes in the bacteriophage interactions with the bacteria, it is necessary to isolate and investigate large numbers of independent resistant variants. Here we describe protocols that have been applied to the study of Pseudomonas aeruginosa and four of its virulent bacteriophages belonging to the Podoviridae and Myoviridae bacteriophage families. Mutations are identified using whole genome sequencing of resistant variants. Phenotypic analyses are performed to describe the changes conferred by the mutations.
    Mots-clés : Bacterial phenotype, Bacteriophages, Complementation, Genome sequencing, LGBMB, MICROBIO.

  • H. Liu, Y. Zhang, Z. Liu, J. Liu, Y. Hauck, J. Liu, H. Dong, J. Liu, X. Zhao, B. Lu, Y. Jiang, G. Vergnaud, C. Pourcel, et K. Wan, « Associations between Mycobacterium tuberculosis Beijing genotype and drug resistance to four first-line drugs: a survey in China », Frontiers of Medicine, vol. 12, nᵒ 1, p. 92-97, 2018.

  • A. Maikova, J. Peltier, P. Boudry, E. Hajnsdorf, N. Kint, M. Monot, I. Poquet, I. Martin-Verstraete, B. Dupuy, et O. Soutourina, « Discovery of new type I toxin–antitoxin systems adjacent to CRISPR arrays in Clostridium difficile », Nucleic Acids Research, févr. 2018.

  • M. Mardirossian, Q. Barrière, T. Timchenko, C. Müller, S. Pacor, P. Mergaert, M. Scocchi, et D. N. Wilson, « Fragments of the non-lytic proline-rich antimicrobial peptide Bac5 kill E. coli cells by inhibiting protein synthesis », Antimicrobial Agents and Chemotherapy, mai 2018.
    Résumé : Unlike most antimicrobial peptides (AMPs), the main mode of action of the subclass of proline-rich antimicrobial peptides (PrAMPs) is not based on disruption of the bacterial membrane. Instead, PrAMPs exploit the inner membrane transporters SbmA and YjiL/MdtM to pass through the bacterial membrane and enter the cytosol of specific Gram-negative bacteria, where they exert an inhibitory effect on protein synthesis. Despite sharing a high proline and arginine content with other characterized PrAMPs, the PrAMP Bac5 has a low sequence identity with them. Here we investigated the mode of action of three N-terminal Bac5 fragments, Bac5 (1-15), Bac5 (1-25) and Bac5 (1-31). We could show that Bac5 (1-25) and Bac5 (1-31) retain excellent antimicrobial activity towards Escherichia coli and low toxicity towards eukaryotic cells, whereas Bac5 (1-15) was inactive. Bac5 (1-25) and Bac5 (1-31) inhibited bacterial protein synthesis in vitro and in vivo Competition assays suggest that the binding site of Bac5 is within the ribosomal tunnel, where it prevents the transition from the initiation to the elongation phase of translation, as reported for other PrAMPs, such as the bovine PrAMP Bac7. Surprisingly, unlike Bac7, Bac5 (1-25) exhibited species-specific inhibition, being an excellent inhibitor of protein synthesis on E. coli ribosomes but a poor inhibitor on Thermus thermophilus ribosomes. This indicates that while Bac5 most likely has an overlapping binding site with Bac7, the mode of interaction is distinct, suggesting that Bac5 fragments may be interesting alternative lead compounds for the development of new antimicrobial agents.
    Mots-clés : MICROBIO, PBI.

  • P. Mergaert, « Role of antimicrobial peptides in controlling symbiotic bacterial populations », Natural Product Reports, févr. 2018.
    Résumé : Covering: up to 2018Antimicrobial peptides (AMPs) have been known for well over three decades as crucial mediators of the innate immune response in animals and plants, where they are involved in the killing of infecting microbes. However, AMPs have now also been found to be produced by eukaryotic hosts during symbiotic interactions with bacteria. These symbiotic AMPs target the symbionts and therefore have a more subtle biological role: not eliminating the microbial symbiont population but rather keeping it in check. The arsenal of AMPs and the symbionts' adaptations to resist them are in a careful balance, which contributes to the establishment of the host-microbe homeostasis. Although in many cases the biological roles of symbiotic AMPs remain elusive, for a number of symbiotic interactions, precise functions have been assigned or proposed to the AMPs, which are discussed here. The microbiota living on epithelia in animals, from the most primitive ones to the mammals, are challenged by a cocktail of AMPs that determine the specific composition of the bacterial community as well as its spatial organization. In the symbiosis of legume plants with nitrogen-fixing rhizobium bacteria, the host deploys an extremely large panel of AMPs - called nodule-specific cysteine-rich (NCR) peptides - that drive the bacteria into a terminally differentiated state and manipulate the symbiont physiology to maximize the benefit for the host. The NCR peptides are used as tools to enslave the bacterial symbionts, limiting their reproduction but keeping them metabolically active for nitrogen fixation. In the nutritional symbiotic interactions of insects and protists that have vertically transmitted bacterial symbionts with reduced genomes, symbiotic AMPs could facilitate the integration of the endosymbiont and host metabolism by favouring the flow of metabolites across the symbiont membrane through membrane permeabilization.
    Mots-clés : MICROBIO, PBI.

  • L. Meyer, G. Coste, S. Sommer, J. Oberto, F. Confalonieri, P. Servant, et C. Pasternak, « DdrI, a CRP family member, acts as a major regulator for adaptation of Deinococcus radiodurans to various stresses », Journal of Bacteriology, avr. 2018.
    Résumé : The DNA damage response gene ddrI encodes a transcription regulator belonging to the CRP (cAMP Receptor Protein) family. Cells devoid of the DdrI protein exhibit a pleiotropic phenotype, including growth defects, sensitivity to DNA damaging agents and to oxidative stress. Here, we show that the absence of DdrI protein also confers sensitivity to heat shock treatment and several genes involved in heat shock response were shown to be up-regulated in a DdrI dependent manner. Interestingly, expression of the E. coli CRP protein partially compensates the absence of the DdrI protein. Microscopic observations of ΔddrI mutant cells revealed an increased proportion of two-tetrads and anucleated cells in the population as compared to the wild-type strain, indicating that DdrI is crucial for completion of cell division and/or chromosome segregation. We show that DdrI is also involved in the megaplasmid MP1 stability and in efficient plasmid transformation by facilitating the maintenance of the incoming plasmid in the cell. The in silico prediction of putative DdrI binding sites in the D. radiodurans genome suggests that hundreds of genes, belonging to several functional groups, may be regulated by DdrI. In addition, DdrI protein absolutely requires cAMP for in vitro binding to specific target sequences, and acts as a dimer. All these data underline the major role of DdrI for D. radiodurans physiology under normal and stress conditions by regulating, both directly and indirectly, a cohort of genes involved in various cellular processes including central metabolism and specific responses to diverse harmful environments.IMPORTANCEDeinococcus radiodurans has been extensively studied to elucidate the molecular mechanisms responsible for its exceptional ability to withstand lethal effects of various DNA-damaging agents. A complex network, including efficient DNA repair, protein protection against oxidation, as well as diverse metabolic pathways, plays a crucial role for its radioresistance. The regulatory networks orchestrating these various pathways are still missing. Our data provide new insights in the crucial contribution of the transcription factor DdrI for the D. radiodurans ability to withstand harmful conditions, including UV radiation, mitomycin C treatment, heat shock and oxidative stress. Finally, we highlight that DdrI is also required for accurate cell division, for maintenance of plasmid replicons, and for central metabolism processes responsible for the overall cell physiology.
    Mots-clés : ARCHEE, BDG, MICROBIO, RBA.

  • B. Molina-Moya, M. Agonafir, S. Blanco, R. Dacombe, M. K. Gomgnimbou, L. Spinasse, M. Gomes-Fernandes, D. G. Datiko, T. Edwards, L. E. Cuevas, J. Dominguez, et C. Sola, « Microbead-based spoligotyping of Mycobacterium tuberculosis from Ziehl-Neelsen-stained microscopy preparations in Ethiopia », Scientific Reports, vol. 8, nᵒ 1, 2018.

  • B. Molina-Moya, M. K. Gomgnimbou, L. Spinasse, J. Obasanya, O. Oladimeji, R. Dacombe, T. Edwards, X. - O. Daragon, L. Lawson, S. T. Abdurrahman, L. E. Cuevas, J. Dominguez, et C. Sola, « Mycobacterium tuberculosis complex genotypes circulating in Nigeria based on spoligotyping obtained from Ziehl-Neelsen stained slides extracted DNA », PLoS neglected tropical diseases, vol. 12, nᵒ 2, p. e0006242, févr. 2018.
    Résumé : METHODS: All State TB control programmes in Nigeria were requested to submit 25-50 smear-positive Ziehl-Neelsen (ZN) stained slides for screening during 2013-2014. DNA was extracted from 929 slides for spoligotyping and drug-resistance analysis using microbead-based flow-cytometry suspension arrays. RESULTS: Spoligotyping results were obtained for 549 (59.1%) of 929 samples. Lineage 4 Cameroon sublineage (L4.6.2) represented half of the patterns, Mycobacterium africanum (L5 and L6) represented one fifth of the patterns, and all other lineages, including other L4 sublineages, represented one third of the patterns. Sublineage L4.6.2 was mostly identified in the north of the country whereas L5 was mostly observed in the south and L6 was scattered. The spatial distribution of genotypes had genetic geographic gradients. We did not obtain results enabling the detection of drug-resistance mutations. CONCLUSION/SIGNIFICANCE: We present the first national snapshot of the M. tuberculosis spoligotypes circulating in Nigeria based on ZN slides. Spoligotyping data can be obtained in a rapid and high-throughput manner with DNA extracted from ZN-stained slides, which may potentially improve our understanding of the genetic epidemiology of TB.
    Mots-clés : IGEPE, MICROBIO.

  • F. Ngadjeua, E. Braud, S. Saidjalolov, L. Iannazzo, D. Schnappinger, S. Ehrt, J. - E. Hugonnet, D. Mengin-Lecreulx, D. P. Patin, M. Ethève-Quelquejeu, M. Fonvielle, et M. Arthur, « Critical impact of peptidoglycan precursor amidation on the activity of L,D-transpeptidases from Enterococcus faecium and Mycobacterium tuberculosis », Chemistry (Weinheim an Der Bergstrasse, Germany), févr. 2018.
    Résumé : The bacterial cell wall peptidoglycan contains unusual L and D amino acids assembled in branched peptides. Insight into the biosynthesis of the polymer has been hampered by limited access to substrates and to suitable polymerization assays. Here we report the full synthesis of the peptide stem of peptidoglycan precursors from two pathogenic bacteria, Enterococcus faecium and Mycobacterium tuberculosis, and the development of a sensitive post-derivatization assay for their cross-linking by L,D-transpeptidases. Access to series of stem peptides showed that amidation of free carboxyl groups is essential for optimal enzyme activity, in particular the amidation of diaminopimelate (DAP) residues for the cross-linking activity of the L,D-transpeptidase LdtMt2 from M. tuberculosis. Accordingly, construction of a conditional mutant established the essentiality of AsnB indicating that this DAP amidotransferase is an attractive target for the development of anti-mycobacterial drugs.
    Mots-clés : Amidation, Amidotransferase, ENVBAC, MICROBIO, Mycobacterium tuberculosis, Peptidoglycan, Transpeptidase.

  • J. R. Osman, G. Fernandes, C. Regeard, C. Jaubert, et M. S. DuBow, « Examination of the Bacterial Biodiversity of Coastal Eroded Surface Soils from the Padza de Dapani (Mayotte Island) », Geomicrobiology Journal, vol. 35, nᵒ 5, p. 355-365, 2018.
    Résumé : To better understand microbial populations present in atypical soil environments, and to discern any relations between these environments and their bacterial communities, we examined the “Padza de Dapani” on the island of Mayotte off the east coast of Africa. This area is not a true (hot) desert, but resembles one in many places due to extensive soil erosion. We collected surface soil samples from five different sites of the Padza de Dapani in Mayotte. We examined bacterial biodiversity using pyrosequencing of PCR-amplified 16S V1–V3 rDNA sequences from total extracted DNA. Our results show that in the acidic (pH 4.6–6), oligotrophic (organic carbon; 0.1–0.7 g/kg of soil) and mineralized (Fe: 18 g/100 g; Al: 12 g/100 g) Dapani Padza soil samples, members of the Actinobacteria and Proteobacteria phyla dominated the bacterial communities, as was also observed in samples from Saudi Arabia hot desert sands.Interestingly, members belonging to the genera Acinetobacter, Arthrobacter and Bacillus were also found to be very abundant in our samples. These were also seen in hot Asian deserts sand samples, such as those from the Gobi (Mongolia) and Taklamaken (China) deserts, thus possibly pointing to microbial populations characteristic of denuded soils.
    Mots-clés : 16S rRNA, Bacteria, biodiversity, LGBMB, MICROBIO, pyrosequencing, soil erosion.

  • A. Pichard-Kostuch, W. Zhang, D. Liger, M. - C. Daugeron, J. Letoquart, I. Li de la Sierra-Gallay, P. Forterre, B. Collinet, H. van Tilbeurgh, et T. Basta, « Structure-function analysis of Sua5 protein reveals novel functional motifs required for the biosynthesis of the universal t6A tRNA modification », RNA (New York, N.Y.), avr. 2018.
    Résumé : N6-threonyl-carbamoyl adenosine (t6A) is a universal tRNA modification found at position 37, next to the anticodon, in almost all tRNAs decoding ANN codons (where N = A, U, G or C). t6A stabilizes the codon-anticodon interaction and hence promotes translation fidelity. The first step of the biosynthesis of t6A, the production of threonyl-carbamoyl adenylate (TC-AMP), is catalyzed by the Sua5/TsaC family of enzymes. While TsaC is a single domain protein, Sua5 enzymes are composed of the TsaC-like domain, a linker and an extra domain called SUA5 of unknown function. In the present study, we report structure-function analysis of Pyrococcus abyssi Sua5 (Pa-Sua5). Crystallographic data revealed binding sites for bicarbonate substrate and pyrophosphate product. The linker of Pa-Sua5 forms a loop structure that folds into the active site gorge and closes it. Using structure-guided mutational analysis we established that the conserved sequence motifs in the linker and the domain-domain interface are essential for the function of Pa-Sua5. We propose that the linker participates actively in the biosynthesis of TC-AMP by binding to ATP/PPi and by stabilizing the N-carboxy-L-threonine intermediate. Hence, TsaC orthologs which lack such a linker and SUA5 domain use different mechanism for TC-AMP synthesis.
    Mots-clés : ARCHEE, B3S, FAAM, MICROBIO, Sua5, t6A37, threonylcarbamoyl adenosine, tRNA modification, TsaC.

  • F. Pompeo, D. Byrne, D. Mengin-Lecreulx, et A. Galinier, « Dual regulation of activity and intracellular localization of the PASTA kinase PrkC during Bacillus subtilis growth », Scientific Reports, vol. 8, nᵒ 1, 2018.

  • E. Schmitt, G. Bourgeois, M. Gondry, et A. Aleksandrov, « Cyclization Reaction Catalyzed by Cyclodipeptide Synthases Relies on a Conserved Tyrosine Residue », Scientific Reports, vol. 8, nᵒ 1, p. 7031, mai 2018.
    Résumé : Cyclodipeptide synthases (CDPSs) form various cyclodipeptides from two aminoacyl tRNAs via a stepwise mechanism with the formation of a dipeptidyl enzyme intermediate. As a final step of the catalytic reaction, the dipeptidyl group undergoes intramolecular cyclization to generate the target cyclodipeptide product. In this work, we investigated the cyclization reaction in the cyclodipeptide synthase AlbC using QM/MM methods and free energy simulations. The results indicate that the catalytic Y202 residue is in its neutral protonated form, and thus, is not likely to serve as a general base during the reaction. We further demonstrate that the reaction relies on the conserved residue Y202 serving as a proton relay, and the direct proton transfer from the amino group to S37 of AlbC is unlikely. Calculations reveal that the hydroxyl group of tyrosine is more suitable for the proton transfer than hydroxyl groups of other amino acids, such as serine and threonine. Results also show that the residues E182, N40, Y178 and H203 maintain the correct conformation of the dipeptide needed for the cyclization reaction. The mechanism discovered in this work relies on the amino groups conserved among the entire CDPS family and, thus is expected to be universal among CDPSs.
    Mots-clés : BIOSYN, MICROBIO.

  • G. Vergnaud, C. Midoux, Y. Blouin, M. Bourkaltseva, V. Krylov, et C. Pourcel, « Transposition Behavior Revealed by High-Resolution Description of Pseudomonas Aeruginosa Saltovirus Integration Sites », Viruses, vol. 10, nᵒ 5, 2018.
    Résumé : Transposable phages, also called saltoviruses, of which the Escherichia coli phage Mu is the reference, are temperate phages that multiply their genome through replicative transposition at multiple sites in their host chromosome. The viral genome is packaged together with host DNA at both ends. In the present work, genome sequencing of three Pseudomonas aeruginosa transposable phages, HW12, 2P1, and Ab30, incidentally gave us access to the location of thousands of replicative integration sites and revealed the existence of a variable number of hotspots. Taking advantage of deep sequencing, we then designed an experiment to study 13,000,000 transposon integration sites of bacteriophage Ab30. The investigation revealed the presence of 42 transposition hotspots adjacent to bacterial interspersed mosaic elements (BIME) accounting for 5% of all transposition sites. The rest of the sites appeared widely distributed with the exception of coldspots associated with low G-C content segments, including the putative O-antigen biosynthesis cluster. Surprisingly, 0.4% of the transposition events occurred in a copy of the phage genome itself, indicating that the previously described immunity against such events is slightly leaky. This observation allowed drawing an image of the phage chromosome supercoiling into four loops.
    Mots-clés : chromosomal domain, deep sequencing, hotspots, imaging, LGBMB, MICROBIO, supercoiling, transposable phages, transposon integration.

  • T. Vourc'h, H. Peerhossaini, J. Léopoldès, A. Méjean, F. Chauvat, et C. Cassier-Chauvat, « Slowdown of surface diffusion during early stages of bacterial colonization », Physical Review E, vol. 97, nᵒ 3, mars 2018.

  • M. Yasmin, G. Refregier, R. T. Siddiqui, R. Iqbal, S. A. Abbasi, et S. Tahseen, « Reverse line probe assay for cheap detection of Single Nucleotide Polymorphisms in Mycobacterium tuberculosis », Tuberculosis (Edinburgh, Scotland), vol. 110, p. 52-55, mai 2018.
    Résumé : More and more Single Nucleotide Polymosrphisms of interest among pathogenic organisms are described with the advent of Whole Genome Sequencing but WGS approach is still too expensive, time consuming, and relying on bioinformatical means that are not available in many developing countries. This study presents a low-cost reverse hybridization line probe technique for detecting SNPs in Mycobacterium tuberculosis. The proposed test is able to detect mutations in the RRDR of rpoB gene in M. tuberculosis with specificity and sensitivity of 98% and 100%, respectively and for an average cost of less than €3 per sample. The technique proved efficient not only on pure DNA samples extracted from culture isolates but also on crude extracts from clinical samples. The flexibility of the platform allows to get it transformed to any kind of test detection, hence, building a bridge between rich countries performing SNP discovery and countries with high burden that can target these SNPs on the collected samples.
    Mots-clés : Global health, IGEPE, Line probe assay, MDR-TB, MICROBIO, Molecular detection of RIF resistance, SNPs detection.


  • S. Al Dahouk, S. Köhler, A. Occhialini, M. P. Jiménez de Bagüés, J. A. Hammerl, T. Eisenberg, G. Vergnaud, A. Cloeckaert, M. S. Zygmunt, A. M. Whatmore, F. Melzer, K. P. Drees, J. T. Foster, A. R. Wattam, et H. C. Scholz, « Brucella spp. of amphibians comprise genomically diverse motile strains competent for replication in macrophages and survival in mammalian hosts », Scientific Reports, vol. 7, p. 44420, mars 2017.
    Résumé : Twenty-one small Gram-negative motile coccobacilli were isolated from 15 systemically diseased African bullfrogs (Pyxicephalus edulis), and were initially identified as Ochrobactrum anthropi by standard microbiological identification systems. Phylogenetic reconstructions using combined molecular analyses and comparative whole genome analysis of the most diverse of the bullfrog strains verified affiliation with the genus Brucella and placed the isolates in a cluster containing B. inopinata and the other non-classical Brucella species but also revealed significant genetic differences within the group. Four representative but molecularly and phenotypically diverse strains were used for in vitro and in vivo infection experiments. All readily multiplied in macrophage-like murine J774-cells, and their overall intramacrophagic growth rate was comparable to that of B. inopinata BO1 and slightly higher than that of B. microti CCM 4915. In the BALB/c murine model of infection these strains replicated in both spleen and liver, but were less efficient than B. suis 1330. Some strains survived in the mammalian host for up to 12 weeks. The heterogeneity of these novel strains hampers a single species description but their phenotypic and genetic features suggest that they represent an evolutionary link between a soil-associated ancestor and the mammalian host-adapted pathogenic Brucella species.
    Mots-clés : LGBMB, MICROBIO.

  • A. K. Alame-Emane, C. Pierre-Audigier, O. C. Aboumegone-Biyogo, A. Nzoghe-Mveang, V. Cadet-Daniel, C. Sola, J. F. Djoba-Siawaya, B. Gicquel, et H. E. Takiff, « The use of GeneXpert remnants for drug resistance profiling and molecular epidemiology of tuberculosis in Libreville, Gabon », Journal of Clinical Microbiology, avr. 2017.
    Résumé : Multidrug (MDR) and extensively drug resistant (XDR) Mycobacterium tuberculosis are major problems in global health. The GeneXpertMTB/RIF (Xpert) rapidly detects resistance to rifampicin (RIF-R), but detection of the additional resistance that defines MDR and XDR-TB, and for molecular epidemiology, specimen cultures and biosafe infrastructure are generally required. We sought to determine whether the remnants of sputa prepared for Xpert could be used directly to find mutations associated with drug resistance and for molecular epidemiology, and thus provide a precise characterization of MDR-TB cases in countries lacking BSL3 facilities for M. tuberculosis cultures. After sputa were processed and run on the Xpert instrument, the leftovers of the samples prepared for Xpert were used for PCR amplification and sequencing or line probe assay to detect mutations associated with resistance to additional drugs, and for molecular epidemiology with spoligotyping and selective MIRU-VNTR. Of 130 sputum samples from Gabon tested with Xpert, 124 yielded interpretable results, of which 21 were determined to be RIF-R (17%). Amplification and sequencing or line probe assay of the Xpert remnants confirmed 18/21 as MDR: 11/116 (9.5%) new and 7/8 (87%) previously treated TB patients. Spoligotyping and MIRU with hypervariable loci identified an MDR Beijing strain present in five samples. We conclude that the remnants of samples processed for Xpert in PCR reactions can be used to find mutations associated with the resistance to the additional drugs that define MDR and XDR-TB, and to study molecular epidemiology without the need for culturing or biosafe infrastructure.
    Mots-clés : IGEPE, MICROBIO.

  • K. Bangpanwimon, J. Sottisuporn, P. Mittraparp-Arthorn, W. Ueaphatthanaphanich, A. Rattanasupar, C. Pourcel, et V. Vuddhakul, « Correction to: CRISPR-like sequences in Helicobacter pylori and application in genotyping », Gut Pathogens, vol. 9, p. 72, 2017.
    Résumé : [This corrects the article DOI: 10.1186/s13099-017-0215-8.].
    Mots-clés : LGBMB, MICROBIO.

  • K. Bangpanwimon, J. Sottisuporn, P. Mittraparp-Arthorn, W. Ueaphatthanaphanich, A. Rattanasupar, C. Pourcel, et V. Vuddhakul, « CRISPR-like sequences in Helicobacter pylori and application in genotyping », Gut Pathogens, vol. 9, p. 65, 2017.
    Résumé : Background: Many bacteria and archaea possess a defense system called clustered regularly interspaced short palindromic repeats (CRISPR) associated proteins (CRISPR-Cas system) against invaders such as phages or plasmids. This system has not been demonstrated in Helicobacter pylori. The numbers of spacer in CRISPR array differ among bacterial strains and can be used as a genetic marker for bacterial typing. Results: A total of 36 H. pylori isolates were collected from patients in three hospitals located in the central (PBH) and southern (SKH) regions of Thailand. It is of interest that CRISPR-like sequences of this bacterium were detected in vlpC encoded for VacA-like protein C. Virulence genes were investigated and the most pathogenic genotype (cagA vacA s1m1) was detected in 17 out of 29 (58.6%) isolates from PBH and 5 out of 7 (71.4%) from SKH. vapD gene was identified in each one isolate from PBH and SKH. CRISPR-like sequences and virulence genes of 20 isolates of H. pylori obtained in this study were analyzed and CRISPR-virulence typing was constructed and compared to profiles obtained by the random amplification of polymorphic DNA (RAPD) technique. The discriminatory power (DI) of CRISPR-virulence typing was not different from RAPD typing. Conclusion: CRISPR-virulence typing in H. pylori is easy and reliable for epidemiology and can be used for inter-laboratory interpretation.
    Mots-clés : CRISPR-like sequences, CRISPR-virulence typing, Helicobacter pylori, LGBMB, MICROBIO, Orphan CRISPR array, vacA-like gene, vlpC gene.

  • Q. Barrière, I. Guefrachi, D. Gully, F. Lamouche, O. Pierre, J. Fardoux, C. Chaintreuil, B. Alunni, T. Timchenko, E. Giraud, et P. Mergaert, « Integrated roles of BclA and DD-carboxypeptidase 1 in Bradyrhizobium differentiation within NCR-producing and NCR-lacking root nodules », Scientific Reports, vol. 7, nᵒ 1, p. 9063, août 2017.
    Résumé : Legumes harbor in their symbiotic nodule organs nitrogen fixing rhizobium bacteria called bacteroids. Some legumes produce Nodule-specific Cysteine-Rich (NCR) peptides in the nodule cells to control the intracellular bacterial population. NCR peptides have antimicrobial activity and drive bacteroids toward terminal differentiation. Other legumes do not produce NCR peptides and their bacteroids are not differentiated. Bradyrhizobia, infecting NCR-producing Aeschynomene plants, require the peptide uptake transporter BclA to cope with the NCR peptides as well as a specific peptidoglycan-modifying DD-carboxypeptidase, DD-CPase1. We show that Bradyrhizobium diazoefficiens strain USDA110 forms undifferentiated bacteroids in NCR-lacking soybean nodules. Unexpectedly, in Aeschynomene afraspera nodules the nitrogen fixing USDA110 bacteroids are hardly differentiated despite the fact that this host produces NCR peptides, suggesting that USDA110 is insensitive to the host peptide effectors and that nitrogen fixation can be uncoupled from differentiation. In agreement with the absence of bacteroid differentiation, USDA110 does not require its bclA gene for nitrogen fixing symbiosis with these two host plants. Furthermore, we show that the BclA and DD-CPase1 act independently in the NCR-induced morphological differentiation of bacteroids. Our results suggest that BclA is required to protect the rhizobia against the NCR stress but not to induce the terminal differentiation pathway.
    Mots-clés : MICROBIO, PBI.

  • A. Boet, G. Jourdain, S. Demontoux, S. Hascoet, P. Tissieres, C. Rucker-Martin, et D. De Luca, « Basic Hemodynamic Monitoring Using Ultrasound or Electrical Cardiometry During Transportation of Neonates and Infants », Pediatric Critical Care Medicine: A Journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies, août 2017.
    Résumé : OBJECTIVES: Electrical cardiometry and heart ultrasound might allow hemodynamic evaluation during transportation of critically ill patients. Our aims were 1) to test feasibility of stroke volume monitoring using electrical cardiometry or ultrasound during transportation and 2) to investigate if transportation impacts on electrical cardiometry and ultrasound reliability. DESIGN: Prospective, pragmatic, feasibility cohort study. SETTING: Mobile ICUs specialized for neonatal and pediatric transportation. PATIENTS: Thirty hemodynamically stable neonates and infants. INTERVENTIONS: Patients enrolled underwent paired stroke volume measurements (180 before/after and 180 during the transfer) by electrical cardiometry (SVEC) and ultrasound (SVUS). MEASUREMENTS AND MAIN RESULTS: No problems or malfunctioning occurred neither with electrical cardiometry nor with ultrasound. Ultrasound lasted on average 90 (10) seconds, while 45 (15) seconds were needed to instigate electrical cardiometry monitoring. Coefficient of variation was higher for SVUS (before/after: 0.57; during: 0.66) than for SVEC (before/after: 0.38; during: 0.36). Correlations between SVEC and SVUS before/after and during the transfer were r equal to 0.57 and r equal to 0.8, respectively (p always < 0.001). Bland-Altman analysis showed that stroke volume tends to be higher if measured by electrical cardiometry. SVEC measured before (5.5 [2.4] mL), during (5.4 [2.4] mL), and after the transfer (5.4 [2.3] mL) are similar (p = 0.955); same applies for SVUS before (2.6 [1.5] mL), during (2.4 [2] mL), and after (2.9 [2] mL) the transfer (p = 0.268). CONCLUSIONS: Basic hemodynamic monitoring is feasible during pediatric and neonatal transportation both with electrical cardiometry and ultrasound. These two techniques show comparable reliability, although stroke volume was higher if measured by electrical cardiometry. The transportation itself does not affect the reliability of stroke volume measurements.
    Mots-clés : ESHR, MICROBIO.

  • C. Bonura, C. Sola, et F. Vitale, « Obituary Pra. Caterina Mammina 1957–2016 », Tuberculosis, vol. 103, p. A1-A2, 2017.

  • M. Bosco, A. Massarweh, S. Iatmanen-Harbi, A. Bouhss, I. Chantret, P. Busca, S. E. H. Moore, et C. Gravier-Pelletier, « Synthesis and biological evaluation of chemical tools for the study of Dolichol Linked Oligosaccharide Diphosphatase (DLODP) », European Journal of Medicinal Chemistry, vol. 125, p. 952-964, janv. 2017.
    Résumé : Citronellyl- and solanesyl-based dolichol linked oligosaccharide (DLO) analogs were synthesized and tested along with undecaprenyl compounds for their ability to inhibit the release of [(3)H]OSP from [(3)H]DLO by mammalian liver DLO diphosphatase activity. Solanesyl (C45) and undecaprenyl (C55) compounds were 50-500 fold more potent than their citronellyl (C10)-based counterparts, indicating that the alkyl chain length is important for activity. The relative potency of the compounds within the citronellyl series was different to that of the solanesyl series with citronellyl diphosphate being 2 and 3 fold more potent than citronellyl-PP-GlcNAc2 and citronellyl-PP-GlcNAc, respectively; whereas solanesyl-PP-GlcNAc and solanesyl-PP-GlcNAc2 were 4 and 8 fold more potent, respectively, than solanesyl diphosphate. Undecaprenyl-PP-GlcNAc and bacterial Lipid II were 8 fold more potent than undecaprenyl diphosphate at inhibiting the DLODP assay. Therefore, at least for the more hydrophobic compounds, diphosphodiesters are more potent inhibitors of the DLODP assay than diphosphomonoesters. These results suggest that DLO rather than dolichyl diphosphate might be a preferred substrate for the DLODP activity.
    Mots-clés : Animals, Biological evaluation, CDG, Diphosphatase, Disubstituted diphosphates, Dolichol, Dolichol Phosphates, ENVBAC, Glycochemistry, Humans, liver, MICROBIO, Monoterpenes, Oligosaccharides, Phosphoric Diester Hydrolases, Phosphoric Monoester Hydrolases, Phosphosugars, Polyisoprenyl Phosphate Sugars, Polyisoprenyl Phosphates, Substrate Specificity.

  • D. A. Braun, J. Rao, G. Mollet, D. Schapiro, M. - C. Daugeron, W. Tan, O. Gribouval, O. Boyer, P. Revy, T. Jobst-Schwan, J. M. Schmidt, J. A. Lawson, D. Schanze, S. Ashraf, J. F. P. Ullmann, C. A. Hoogstraten, N. Boddaert, B. Collinet, G. Martin, D. Liger, S. Lovric, M. Furlano, I. C. Guerrera, O. Sanchez-Ferras, J. F. Hu, A. - C. Boschat, S. Sanquer, B. Menten, S. Vergult, N. De Rocker, M. Airik, T. Hermle, S. Shril, E. Widmeier, H. Y. Gee, W. - I. Choi, C. E. Sadowski, W. L. Pabst, J. K. Warejko, A. Daga, T. Basta, V. Matejas, K. Scharmann, S. D. Kienast, B. Behnam, B. Beeson, A. Begtrup, M. Bruce, G. - S. Ch'ng, S. - P. Lin, J. - H. Chang, C. - H. Chen, M. T. Cho, P. M. Gaffney, P. E. Gipson, C. - H. Hsu, J. A. Kari, Y. - Y. Ke, C. Kiraly-Borri, W. - M. Lai, E. Lemyre, R. O. Littlejohn, A. Masri, M. Moghtaderi, K. Nakamura, F. Ozaltin, M. Praet, C. Prasad, A. Prytula, E. R. Roeder, P. Rump, R. E. Schnur, T. Shiihara, M. D. Sinha, N. A. Soliman, K. Soulami, D. A. Sweetser, W. - H. Tsai, J. - D. Tsai, R. Topaloglu, U. Vester, D. H. Viskochil, N. Vatanavicharn, J. L. Waxler, K. J. Wierenga, M. T. F. Wolf, S. - N. Wong, S. A. Leidel, G. Truglio, P. C. Dedon, A. Poduri, S. Mane, R. P. Lifton, M. Bouchard, P. Kannu, D. Chitayat, D. Magen, B. Callewaert, H. van Tilbeurgh, M. Zenker, C. Antignac, et F. Hildebrandt, « Mutations in KEOPS-complex genes cause nephrotic syndrome with primary microcephaly », Nature Genetics, août 2017.
    Résumé : Galloway-Mowat syndrome (GAMOS) is an autosomal-recessive disease characterized by the combination of early-onset nephrotic syndrome (SRNS) and microcephaly with brain anomalies. Here we identified recessive mutations in OSGEP, TP53RK, TPRKB, and LAGE3, genes encoding the four subunits of the KEOPS complex, in 37 individuals from 32 families with GAMOS. CRISPR-Cas9 knockout in zebrafish and mice recapitulated the human phenotype of primary microcephaly and resulted in early lethality. Knockdown of OSGEP, TP53RK, or TPRKB inhibited cell proliferation, which human mutations did not rescue. Furthermore, knockdown of these genes impaired protein translation, caused endoplasmic reticulum stress, activated DNA-damage-response signaling, and ultimately induced apoptosis. Knockdown of OSGEP or TP53RK induced defects in the actin cytoskeleton and decreased the migration rate of human podocytes, an established intermediate phenotype of SRNS. We thus identified four new monogenic causes of GAMOS, describe a link between KEOPS function and human disease, and delineate potential pathogenic mechanisms.
    Mots-clés : ARCHEE, B3S, FAAM, MICROBIO.

  • A. Breton, A. Novikov, R. Martin, P. Tissieres, et M. Caroff, « Structural and biological characteristics of different forms of V. filiformis lipid A: use of MS to highlight structural discrepancies », Journal of Lipid Research, vol. 58, nᵒ 3, p. 543-552, mars 2017.
    Résumé : Vitreoscilla filiformis is a Gram-negative bacterium isolated from spa waters and described for its beneficial effects on the skin. We characterized the detailed structure of its lipopolysaccharide (LPS) lipid A moiety, an active component of the bacterium that contributes to the observed skin activation properties. Two different batches differing in postculture cell recovery were tested. Chemical analyses and mass spectra, obtained before and after mild-alkali treatments, revealed that these lipids A share the common bisphosphorylated β-(1→6)-linked d-glucosamine disaccharide with hydroxydecanoic acid in an amide linkage. Short-chain FAs, hydroxydecanoic and dodecanoic acid, were found in a 2:1 ratio. The two lipid A structures differed by the relative amount of the hexa-acyl molecular species and phosphoethanolamine substitution of the phosphate groups. The two V. filiformis LPS batches induced variable interleukin-6 and TNF-α secretion by stimulated myelomonocytic THP-1 cells, without any difference in reactive oxygen species production or activation of caspase 3/7. Other different well-known highly purified LPS samples were characterized structurally and used as standards. The structural data obtained in this work explain the low inflammatory response observed for V. filiformis LPS and the previously demonstrated beneficial effects on the skin.
    Mots-clés : cytokines, ESHR, lipid biochemistry, lipopolysaccharide, Mass Spectrometry, MICROBIO, skin, Toll-like receptor, V. filiformis.

  • S. Bury-Moné et B. Sclavi, « Stochasticity of gene expression as a motor of epigenetics in bacteria: from individual to collective behavior », Research in Microbiology, avr. 2017.
    Résumé : Measuring gene expression at the single cell and single molecule level has recently made possible the quantitative measurement of stochasticity of gene expression. This enables identification of the probable sources and roles of noise. Stochastic gene expression can result in bacterial population heterogeneity, offering specific advantages for fitness and survival in various environments. This trait is therefore selected during the evolution of the species, and is consequently regulated by specific genetic network architecture. Examples exist in stress-response mechanisms, as well as in infection and pathogenicity strategies, pointing to advantages for multicellularity of bacterial populations.
    Mots-clés : ACTINO, Behavior, Bi-stability, Epigenetics, gene expression, MICROBIO, Multicellularity, regulatory networks, Stochasticity.

  • C. Cassier-Chauvat, V. Dive, et F. Chauvat, « Cyanobacteria: photosynthetic factories combining biodiversity, radiation resistance, and genetics to facilitate drug discovery », Applied Microbiology and Biotechnology, vol. 101, nᵒ 4, p. 1359-1364, févr. 2017.
    Résumé : Cyanobacteria are ancient, abundant, and widely diverse photosynthetic prokaryotes, which are viewed as promising cell factories for the ecologically responsible production of chemicals. Natural cyanobacteria synthesize a vast array of biologically active (secondary) metabolites with great potential for human health, while a few genetic models can be engineered for the (low level) production of biofuels. Recently, genome sequencing and mining has revealed that natural cyanobacteria have the capacity to produce many more secondary metabolites than have been characterized. The corresponding panoply of enzymes (polyketide synthases and non-ribosomal peptide synthases) of interest for synthetic biology can still be increased through gene manipulations with the tools available for the few genetically manipulable strains. In this review, we propose to exploit the metabolic diversity and radiation resistance of cyanobacteria, and when required the genetics of model strains, for the production and radioactive ((14)C) labeling of bioactive products, in order to facilitate the screening for new drugs.
    Mots-clés : B2CYA, Biodiversity, Cyanobacteria, MICROBIO, Peptide Synthases, photosynthesis, Radioactive labeling, Secondary metabolites, Toxins.

  • T. M. Chong, J. - W. Chen, W. - S. See-Too, C. - Y. Yu, G. - Y. Ang, Y. L. Lim, W. - F. Yin, C. Grandclément, D. Faure, Y. Dessaux, et K. - G. Chan, « Phenotypic and genomic survey on organic acid utilization profile of Pseudomonas mendocina strain S5.2, a vineyard soil isolate », AMB Express, vol. 7, nᵒ 1, p. 138, déc. 2017.
    Résumé : Root exudates are chemical compounds that are released from living plant roots and provide significant energy, carbon, nitrogen and phosphorus sources for microbes inhabiting the rhizosphere. The exudates shape the microflora associated with the plant, as well as influences the plant health and productivity. Therefore, a better understanding of the trophic link that is established between the plant and the associated bacteria is necessary. In this study, a comprehensive survey on the utilization of grapevine and rootstock related organic acids were conducted on a vineyard soil isolate which is Pseudomonas mendocina strain S5.2. Phenotype microarray analysis has demonstrated that this strain can utilize several organic acids including lactic acid, succinic acid, malic acid, citric acid and fumaric acid as sole growth substrates. Complete genome analysis using single molecule real-time technology revealed that the genome consists of a 5,120,146 bp circular chromosome and a 252,328 bp megaplasmid. A series of genetic determinants associated with the carbon utilization signature of the strain were subsequently identified in the chromosome. Of note, the coexistence of genes encoding several iron-sulfur cluster independent isoenzymes in the genome indicated the importance of these enzymes in the events of iron deficiency. Synteny and comparative analysis have also unraveled the unique features of D-lactate dehydrogenase of strain S5.2 in the study. Collective information of this work has provided insights on the metabolic role of this strain in vineyard soil rhizosphere.
    Mots-clés : Carbon utilization enzymes, Grapevine exudates, MICROBIO, Organic acids, PBI, Pseudomonas mendocina, Single molecule real-time (SMRT) sequencing, Vineyard soil.

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