Genomics of Microbial Pathogens - CNRS URA2171  


  HEADDr KUNST Frank / fkunst@pasteur.fr
  MEMBERSALBERT-WEISSENBERGER Christiane / Dr BROCHET Mathieu / Dr BUCHRIESER Carmen / Dr CAZALET Christel / COUVE Elisabeth / DA CUNHA Violette
DERVINS-RAVAULT Delphine / Dr GLASER Philippe / Dr GOMEZ Laura / Dr JULES Matthieu / LOMMA Mariella/ MARIN Mickaël / MOURIER Claude / RUSNIOK Christophe / Dr SAHR Tobias / SAINT-MARTIN Françoise


  Annual Report

The research aim of the Unit is to better understand the evolution and the adaptation of the opportunistic bacterial pathogens Listeria monocytogenes, Legionella pneumophila and Streptococcus agalactiae to the host and to the environment.

The genus Listeria (teams C. Buchrieser, P. Glaser)

In collaboration with the German Network PathGenoMik we have analyzed the complete genome sequences of representative isolates of all known Listeria species. Additionally, more than 400 Listeria strains of different origins have been compared by DNA array hybridization. Apparently lower virulence of some strains may be correlated with missing genes, encoding surface proteins and internalins. This information is further exploited to gain a better understanding of evolution and virulence within the genus Listeria.

The genus Legionella (team C. Buchrieser)

The genus Legionella comprises ~50 species, including the human pathogens L.  pneumophila and L. longbeachae the causative agents of Legionnaires’ disease. In order to better understand their virulence strategies we used comparative genomics by hybridization. Analysis of 217 L. pneumophila and 32 Legionella sp. identified a globally distributed epidemic clone that emerged within a highly diverse species. Complete genome sequencing, analysis and comparison of several L. pneumophila strains and Legionella species is now under way to get deeper insight into evolution of virulence and genome plasticity of the genus. As a second approach to understand virulence, we studied LqsR, a newly identified regulator implicated in the life cycle dependent gene expression and virulence of L. pneumophila. To elucidate the complex regulatory network governing virulence of L. pneumophila, we characterize the LetA/LetS system and 2 small non-coding RNAs putatively involved. Furthermore, we are functionally characterizing certain newly identified putative virulence factors, in particular eukaryotic-like proteins.

The genus Streptococcus (team P. Glaser)

It comprises more than 40 species widely distributed among men and animals. S. agalactiae, a colonizer of the gastrointestinal tract, is the major cause of neonatal infections. Comparative genomics and biodiversity studies of a representative panel of Streptococcus isolates revealed a mosaic genome organization with a conserved backbone, 14 genome islands and a high variability of genes encoding surface components. The evolutionary history of the human strains was reconstructed. These strains diversified from a recent common ancestor by exchanging large chromosomal regions from unrelated strains. Two islands were demonstrated to represent a new class of transposase dependent conjugative transposons. The cell surface plays a major role in the interaction with the host. To understand its biogenesis and to identify vaccine candidates, we developed a high throughput screening procedure of insertion mutants and natural isolates using biological markers such as surface polysaccharides and protein antigens.

Keywords: genomics, comparative genomics, evolution, transcriptome, pathogenic bacteria, virulence, regulation



  Publications

Albert-Weissenberger, C., C. Cazalet, Buchrieser C (2007). Legionella pneumophila - a human pathogen that co-evolved with fresh water protozoa. Cell Mol Life Sci 64:432-48. PMID: 17192810.

Brochet M, Couvé E, Zouine M, Poyart C, Glaser P (2007). A naturally occurring gene amplification leading to sulfonamide and trimethoprim resistance in Streptococcus agalactiae. J Bacteriol. Nov 16; [Epub ahead of print]. PMID: 18024520.

Cazalet C, Jarraud S, Ghavi-Helm Y, Allignet J, Kunst F, Glaser P, Etienne J, Buchrieser C. Multi-genome analysis identifies a worldwide-distributed epidemic Legionella pneumophila clone that emerged within a highly diverse species. Genome Research. Accepted for publication.

Severino P, Dussurget O, Vencio RZ, Dumas E, Garrido P, Padilla G, Piveteau P, Lemaitre JP, Kunst F, Glaser P, Buchrieser C (2007). Comparative transcriptome analysis of Listeria monocytogenes strains of the two major lineages reveals differences in virulence, cell wall and stress response. Appl Environ Microbiol. 73 : 6078-6088. PMID: 17704270.

Tiaden A, Spirig T, Weber SS, Bruggemann H, Bosshard R, Buchrieser C, Hilbi H (2007). The Legionella pneumophila response regulator LqsR promotes host cell interactions as an element of the virulence regulatory network controlled by RpoS and LetA. Cell Microbiol. 9 : 2903-2920.



  Web Site

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Activity Reports 2007 - Institut Pasteur
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