Microbiology Department Activity Report

The Department of Microbiology includes 8 Research Units, 2 Provisional Units, 1 Five-year groups, 2 Laboratories. It also hosts 3 collections of micro-organisms, 5 national reference centers, and 2 WHO collaborative centers.

The scientists of this Department study various micro-organisms (bacteria and archae) and their viruses, as model systems for fundamental studies (genomics, genetics, metabolism,…) and to elucidate the mechanisms that allow some of them to be virulent and to escape from the immune system from the host and antibiotics. This work allows a better understanding of their lifestyle and their interactions with the environment. The comprehension of the molecular mechanisms of virulence is essential for the development of new diagnostic tools and new therapies to treat the bacterial infections (antibiotics and vaccines).

EVENTS

Selected highlights of the Department of Microbiology published in 2010 are listed below.

- Gram-negative bacteria secrete folded proteins via the type II secretion systems (T2SS). These complex machineries assemble inner membrane pilin subunits into fibers that drive the protein secretion in a piston-like manner. Using structural modeling and extensive functional validation, the FRANCETIC's team determined the detailed structure of the Klebsiella oxytoca T2SS pilus. The PulG subunits in this fiber are organized as a right-handed helix. The key assembly determinants, localized at the interface between adjacent PulG protomers, are conserved in the major T2S pilin family, supporting the general relevance of this model for T2SS pilus structure.

- Homologous recombination events between circular chromosomes can generate dimers which, in Escherichia coli, are converted to monomers by two paralogous site-specific tyrosine recombinases of the Xer family (XerC/D). Archaea have circular chromosomes and an active homologous recombination system and should therefore resolve chromosome dimers. The FORTERRE's team have shown that chromosome resolution in Archae is also mediated by XerC/D homologue, XerA, although Archaea and Bacteria use a completely different set of proteins for chromosome replication.

- Inducible vancomycin resistance in enterococci is due to a sophisticated mechanism that combines synthesis of cell wall peptidoglycan precursors with low affinity for glycopeptides and elimination of the normal target precursors. The COURVALIN's team demonstrated that tight regulation of resistance expression drastically reduces the biological cost associated with vancomycin resistance in Enterococcus spp. and accounts for the widespread dissemination of these strains. These findings are in agreement with the observation that regulation of expression is common in horizontally acquired resistance and represents an efficient evolutionary pathway for resistance determinants to become selectively neutral.

- Plague is a devastating pandemic disease caused by Yersinia pestis. Using extensive genome comparisons and mutation discovery on a global strain collection, a multinational team, which included the Yersinia Research Unit headed by E. CARNIEL, showed that Y. pestis originated in or near China. This work allowed to reconstruct the routes and time frame of the different plague waves out of China (which fitted with historical data). It also demonstrated that all existant Y. pestis isolates found in each country represent a unique import event.

- Streptococcus agalactiae (Group B Streptococci, GBS) is the major cause of human neonatal meningitis. A single clone, GBS ST-17, is strongly associated with a deadly form of the infection called late-onset disease (LOD), which is characterized by meningitis in infants after the first week of life. The teams of C. POYART (INSERM), M. LECUIT (IP) and P. TRIEU-CUOT (IP) have identified a novel ST-17-specific surface-anchored protein designated hypervirulent GBS adhesin (HvgA) which is required for GBS hypervirulence. HvgA is a critical virulence trait of GBS in the neonatal context and stands as a promising target for the development of novel diagnostic and antibacterial strategies.

The department is involved in teaching activities within the IP campus with 2 senior scientists being in charge of the courses of “General Microbiology” and of Medical Bacteriology.

Publications

The scientists of the department were associated to 85 articles in 2010, among which :

1. Bahlawane, C., C. Dian, C. Muller, A. Round, C. Fauquant, K. Schauer, H. de Reuse, L. Terradot, and I. Michaud-Soret. 2010. Structural and mechanistic insights into Helicobacter pylori NikR activation. Nucleic Acids Res. 38:3106-18.

2. Bonis, M., C. Ecobichon, S. Guadagnini, M. C. Prevost, and I. G. Boneca. 2010. A M23B family metallopeptidase of Helicobacter pylori required for cell shape, pole formation and virulence. Mol. Microbiol. 78:809-19.

3. Bourhy, P., L. Collet, S. Clement, M. Huerre, P. Ave, C. Giry, F. Pettinelli, and M. Picardeau. 2010. Isolation and characterization of new Leptospira genotypes from patients in Mayotte (Indian Ocean). PLoS Negl. Trop. Dis. 4:e724.

4. Campos, M., M. Nilges, D. A. Cisneros, and O. Francetic. 2010. Detailed structural and assembly model of the type II secretion pilus from sparse data. Proc. Natl. Acad. Sci. USA 107:13081-6.

5. Cortez, D., S. Quevillon-Cheruel, S. Gribaldo, N. Desnoues, G. Sezonov, P. Forterre, and M. C. Serre. 2010. Evidence for a Xer/dif system for chromosome resolution in archaea. PLoS Genet. 6:e1001166.

6. Foucault, M. L., F. Depardieu, P. Courvalin, and C. Grillot-Courvalin. 2010. Inducible expression eliminates the fitness cost of vancomycin resistance in enterococci. Proc. Natl. Acad. Sci. USA 107:16964-9.

7. Geny, B., A. Grassart, M. Manich, G. Chicanne, B. Payrastre, N. Sauvonnet, and M. R. Popoff. 2010. Rac1 inactivation by lethal toxin from Clostridium sordellii modifies focal adhesions upstream of actin depolymerization. Cell. Microbiol. 12:217-32.

8. Korea, C. G., R. Badouraly, M. C. Prevost, J. M. Ghigo, and C. Beloin. 2010. Escherichia coli K-12 possesses multiple cryptic but functional chaperone-usher fimbriae with distinct surface specificities. Environ. Microbiol. 12:1957-77.

9. Morelli, G., Y. Song, C. J. Mazzoni, M. Eppinger, P. Roumagnac, D. M. Wagner, M. Feldkamp, B. Kusecek, A. J. Vogler, Y. Li, Y. Cui, N. R. Thomson, T. Jombart, R. Leblois, P. Lichtner, L. Rahalison, J. M. Petersen, F. Balloux, P. Keim, T. Wirth, J. Ravel, R. Yang, E. Carniel, and M. Achtman. 2010. Yersinia pestis genome sequencing identifies patterns of global phylogenetic diversity. Nat. Genet. 42:1140-3.

10. Soutourina, O., S. Dubrac, O. Poupel, T. Msadek, and I. Martin-Verstraete. 2010. The pleiotropic CymR regulator of Staphylococcus aureus plays an important role in virulence and stress response. PLoS Path. 6:e1000894.

11. Tazi, A., O. Disson, S. Bellais, A. Bouaboud, N. Dmytruk, S. Dramsi, M. Y. Mistou, H. Khun, C. Mechler, I. Tardieux, P. Trieu-Cuot, M. Lecuit, and C. Poyart. 2010. The surface protein HvgA mediates group B streptococcus hypervirulence and meningeal tropism in neonates. J. Exp. Med. 207:2313-22.