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Accueil > Départements > Microbiologie > Olga SOUTOURINA : ARNs régulateurs chez les Clostridies



  • 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, vol. 46, nᵒ 9, p. 4733-4751, mai 2018.
    Résumé : Clostridium difficile, a major human enteropathogen, must cope with foreign DNA invaders and multiple stress factors inside the host. We have recently provided an experimental evidence of defensive function of the C. difficile CRISPR (clustered regularly interspaced short palindromic repeats)-Cas (CRISPR-associated) system important for its survival within phage-rich gut communities. Here, we describe the identification of type I toxin-antitoxin (TA) systems with the first functional antisense RNAs in this pathogen. Through the analysis of deep-sequencing data, we demonstrate the general co-localization with CRISPR arrays for the majority of sequenced C. difficile strains. We provide a detailed characterization of the overlapping convergent transcripts for three selected TA pairs. The toxic nature of small membrane proteins is demonstrated by the growth arrest induced by their overexpression. The co-expression of antisense RNA acting as an antitoxin prevented this growth defect. Co-regulation of CRISPR-Cas and type I TA genes by the general stress response Sigma B and biofilm-related factors further suggests a possible link between these systems with a role in recurrent C. difficile infections. Our results provide the first description of genomic links between CRISPR and type I TA systems within defense islands in line with recently emerged concept of functional coupling of immunity and cell dormancy systems in prokaryotes.
    Mots-clés : ARNCLO, MICROBIO.


  • J. R. Garneau, O. Sekulovic, B. Dupuy, O. Soutourina, M. Monot, et L. - C. Fortier, « High Prevalence and Genetic Diversity of Large phiCD211 (phiCDIF1296T)-Like Prophages in <i>Clostridioides difficile</i> », Applied and Environmental Microbiology, vol. 84, nᵒ 3, p. e02164-17, nov. 2017.

  • N. Kint, C. Janoir, M. Monot, S. Hoys, O. Soutourina, B. Dupuy, et I. Martin-Verstraete, « The alternative sigma factor σ(B) plays a crucial role in adaptive strategies of Clostridium difficile during gut infection », Environmental Microbiology, févr. 2017.
    Résumé : Clostridium difficile is a major cause of diarrhoea associated with antibiotherapy. Exposed to stresses in the gut, C. difficile can survive by inducing protection, detoxification and repair systems. In several firmicutes, most of these systems are controlled by the general stress response involving σ(B) . In this work, we studied the role of σ(B) in the physiopathology of C. difficile. We showed that the survival of the sigB mutant during the stationary phase was reduced. Using a transcriptome analysis, we showed that σ(B) controls the expression of ∼25% of genes including genes involved in sporulation, metabolism, cell surface biogenesis and the management of stresses. By contrast, σ(B) does not control toxin gene expression. In agreement with the up-regulation of sporulation genes, the sporulation efficiency is higher in the sigB mutant than in the wild-type strain. sigB inactivation also led to increased sensitivity to acidification, cationic antimicrobial peptides, nitric oxide and ROS. In addition, we showed for the first time that σ(B) also plays a crucial role in oxygen tolerance in this strict anaerobe. Finally, we demonstrated that the fitness of colonisation by the sigB mutant is greatly affected in a dixenic mouse model of colonisation when compared to the wild-type strain.
    Mots-clés : ARNCLO, MICROBIO.

  • J. Peltier et O. Soutourina, « Identification of c-di-GMP-Responsive Riboswitches », Methods in Molecular Biology (Clifton, N.J.), vol. 1657, p. 377-402, 2017.
    Résumé : Bis-(3'-5')-cyclic dimeric guanosine monophosphate (c-di-GMP) is an important signaling molecule for community behavior control, cell morphogenesis, and virulence in bacteria. In addition to protein effectors, this second messenger binds RNA molecules that act as riboswitches to control target gene expression. In this chapter, we describe a method for experimental validation of the functionality of c-di-GMP-responsive riboswitches and the analysis of c-di-GMP control of target gene expression by qRT-PCR and Northern blot. This procedure can be used for the studies of in silico-predicted riboswitch candidates, as well as a targeted experimental approach for exploring the data from next-generation sequencing. The examples on the analysis of type I and type II c-di-GMP-responsive riboswitches in Clostridium difficile are provided to illustrate the application of the method.
    Mots-clés : ARNCLO, c-di-GMP, MICROBIO, Northern blot, Premature termination of transcription, qRT-PCR, Riboswitches, Target gene.

  • O. Soutourina, « RNA-based control mechanisms of Clostridium difficile », Current Opinion in Microbiology, vol. 36, p. 62-68, févr. 2017.
    Résumé : Clostridium difficile (CD)-associated diarrhoea is currently the most prevalent nosocomial diarrhoea worldwide. Many characteristics of CD pathogenicity remain poorly understood. Recent data strongly indicate the importance of an RNA network for the control of gene expression in CD. More than 200 regulatory RNAs have been identified by deep sequencing and targeted approaches, including Hfq-dependent trans riboregulators, cis-antisense RNAs, CRISPR RNAs, and c-di-GMP-responsive riboswitches. These regulatory RNAs are involved in the control of major processes in the CD infection cycle, for example motility, biofilm formation, adhesion, sporulation, stress response, and defence against bacteriophages. We will discuss recent advances in elucidation of the original features of RNA-based mechanisms in this important enteropathogen. This knowledge may pave the way for further discoveries in this emergent field.
    Mots-clés : ARNCLO, MICROBIO.
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Selection of publications before 2017

- Dubois T, Dancer-Thibonnier M, Monot M, Hamiot A, Bouillaut L, Soutourina O, Martin-Verstraete I, and Dupuy B. Control of Clostridium difficile physiopathology in response to cysteine availability. (2016). Infection and immunity 84(8) : 2389-2405.

- Boudry P, Semenova E, Monot M, Datsenko K, Lopatina A, Sekulovic O, Ospina-Bedoya M, Fortier L-C, Severinov K, Dupuy B, Soutourina O.* Function of the CRISPR-Cas system of the human pathogen Clostridium difficile. (2015). mBio 6(5) : e01112-15.

- Rosinski-Chupin I.§, Soutourina O§, Martin-Verstraete I. Riboswitch discovery by combining RNA-seq and Genome-Wide identification of transcriptional start sites. (2014). Methods in Enzymology. Vol. 549 : 3-27. §Equal contribution.

- Boudry P, Gracia C, Monot M, Caillet J, Saujet L, Hajnsdorf E, Dupuy B, Martin-Verstraete I, Soutourina O.* Pleiotropic Role of the RNA Chaperone Protein Hfq in the Human Pathogen Clostridium difficile. (2014). J Bacteriol. 196(18):3234-48.

- El Meouche I., Peltier J., Monot M., Soutourina O., Pestel-Caron M., Dupuy B., Pons J-L. Characterization of the SigD regulon of C. difficile and its positive control of toxin production through the regulation of tcdR. (2013). PLoS One. 8(12) : e83748.

- Saujet L., Pereira F.C., Soutourina O., Shelyakin P., Monot M., Gelfand M., Dupuy B., Henriques A. O. and Martin-Verstraete I. Genome-wide Analysis of Cell type-specific Gene Transcription during Spore Formation in Clostridium difficile. (2013). PLoS Genetics. 9(10) : e1003756.

- Soutourina O.*, Monot, M., Boudry, P., Saujet, L., Pichon, C., Sismeiro, O., Semenova, E., Severinov, K., Le Bouguenec, C., Coppée, J.-Y., Dupuy, B. and Martin-Verstraete, I. Genome-wide identification of regulatory RNAs in the human pathogen Clostridium difficile. (2013). PLoS Genetics. 9(5) :e1003493.

- Shepard W, Soutourina O, Courtois E, England P, Haouz A, Martin-Verstraete I. Insights into the Rrf2 Repressor Family : The Structure of CymR, the Global Cysteine Regulator of Bacillus subtilis. (2011). FEBS J. 278(15):2689-701.

- Saujet L, Monot M, Dupuy B, Soutourina O, Martin-Verstraete I. The key sigma factor of transition phase, SigH, controls sporulation, metabolism and virulence factor expression in Clostridium difficile. (2011). Journal of Bacteriology. 193(13) : 3186-3196.

- Soutourina, O.*, Dubrac, S., Poupel, O., Msadek, T. and Martin-Verstraete, I. The Pleiotropic CymR Regulator of Staphylococcus aureus Plays an Important Role in Virulence and Stress Response. (2010). PLoS Pathogens. 6(5) :e1000894.

- Soutourina, O.*, Poupel, O., Coppée, JY., Danchin, A., Msadek, T. and Martin-Verstraete I. CymR, the master regulator of cysteine metabolism in Staphylococcus aureus, controls human sulphur sources utilization and plays a role in biofilm formation (2009). Mol Microbiol. 73(2) :194-211.

- André, G., Even, S., Putzer, H., Burguière, P., Danchin, A., Martin-Verstraete, I. and Soutourina, O*. S-box and T-box riboswitches and antisense RNA control a sulfur metabolic operon of Clostridium acetobutylicum. (2008). Nucleic Acids Res. 36(18):5955-69. 69 citations.

* corresponding author

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