|Biology of Intracellular Bacteria - CNRS URA2171|
|HEAD||Dr BUCHRIESER Carmen / firstname.lastname@example.org|
|MEMBERS||DERVINS-RAVAULT Delphine / Dr GOMEZ-VALERO Laura / LOMMA Mariella/ LOZA CORREA Maria Guadalupe / MERAULT Nathalie / Dr NORA Tamara / Dr ROLANDO Monica / RUSNIOK Christophe / Dr SAHR Tobias / ETIENNE Annie
Legionnaires’ disease is an important epidemic, nosocomial, or community acquired disease caused by Legionella pneumophila and Legionella longbeachae. A particular feature of Legionella is its dual host system allowing the intracellular growth in aquatic protozoa and during infection in human alveolar macrophages. We are studying three aspects of the biology of these intracellular pathogens.
Biodiversity of L. pneumophila and the genus Legionella
The genus Legionella comprises ~50 species, but L .pneumophila Sg1 is associated with 90% of human disease. In order to better understand the virulence strategies of L. pneumophila we used comparative genomics by hybridization. Analysis of over 200 L. pneumophila and 32 Legionella sp. uncovered a high conservation of virulence- and eukaryotic-like genes indicating strong environmental selection pressures for their preservation. Surprisingly, the LPS gene cluster determining Sg1 was present in diverse genomic backgrounds, strongly implicating the LPS of Sg1 itself as a principal cause of the high prevalence of Sg1 strains in human disease and suggesting that the LPS cluster can be transferred horizontally. Genomic analysis also revealed that L. pneumophila is a genetically diverse species, in part due to horizontal gene transfer of mobile genetic elements. However, the genomic background also plays a role in disease causation as demonstrated by the identification of a globally distributed epidemic strain exhibiting the genotype of the sequenced L. pneumophila strain Paris. 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.
Regulation of the adaptation of Legionella to the host and the environment
To understand the regulatory networks that allow L. pneumophila to adapt to the environment and the host, we investigate the life cycle dependent gene regulation. We characterized two small ncRNAs, RsmY and RsmZ that link the LetA/LetS and CsrA regulatory networks and showed that they are crucial for the L. pneumophila life cycle switch and for L. pneumophila virulence. RsmY/RsmZ double mutants show a drastic defect in intracellular growth in A. castellanii, and in human macrophages. LetA activates transcription of RsmY and RsmZ, which then sequester CsrA and abolish its post-transcriptional repressive activity. However, the RsmYZ-CsrA pathway appears not to be the main or only regulatory circuit governing flagella synthesis. We suggest that rather RpoS and LetA, by influencing LetE and probably cyclic-di-GMP levels, regulate motility in L. pneumophila
Host-pathogen interactions, with special focus on eukaryotic like proteins
Genome analysis identified a high number and variety of eukaryotic-like proteins probably able to interfere in different steps of the infectious cycle by mimicking functions of eukaryotic proteins. Thus, we are functionally characterizing certain newly identified eukaryotic-like proteins, which are putative virulence factors.
Keywords: comparative genomics, transcriptome, Legionella, virulence, regulation
Brüggemann H, Hagman A, Jules M, Sismeiro O, Dillies MA, Gouyette C, Kunst F, Steinert M, Heuner K, Coppee JY and C Buchrieser (2006) Virulence strategies for infecting phagocytes deduced from the in vivo transcriptional program of Legionella pneumophila. Cell Microbiol 8(8):1228-40.
Brüggemann H, Cazalet C and C Buchrieser (2006) Adaptation of Legionella pneumophila to the host environment: role of protein secretion, effectors and eukaryotic-like proteins Curr Opin Microbiol 9(1):86-94.
Tiaden A, Spirig T, Weber SS, Brüggemann H, Bosshard R, Buchrieser C and H Hilbi (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.
Cazalet C, Jarraud S, Ghavi-Helm Y, Kunst F, Glaser P, Etienne J and C Buchrieser (2008). Multi-genome analysis identifies a worldwide-distributed epidemic Legionella pneumophila clone that emerged within a highly diverse species. Genome Res 18(3):431-41.
Sahr T, Brüggemann H, Jules M, Lomma M, Albert-Weissenberger C, Cazalet C, Buchrieser C. (2009) Two small ncRNAs jointly govern virulence and transmission in Legionella pneumophila. Mol Microbiol. 72(3):741-762
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