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.

Genetic basis of L. pneumophila and L. longbeachae

L. pneumophila is mainly found in natural and artificial water circuits while L. longbeachae is mainly present in soil. Under the appropriate conditions both species are human pathogens, capable of causing Legionnaires' disease. We sequenced and analyzed four L. longbeachae genomes, one complete genome sequence of L. longbeachae strain NSW150 serogroup (Sg) 1, and three draft genome sequences belonging to Sg1 and Sg2. The genome organization and gene content of the four L. longbeachae genomes are highly conserved, indicating strong pressure for niche adaptation. Analysis and comparison of L. longbeachae strain NSW150 with L. pneumophila revealed that the interaction with host cells shows distinct features as L. longbeachae possesses a unique repertoire of putative Dot/Icm type IV secretion system substrates, eukaryotic-like and eukaryotic domain proteins, and encodes additional secretion systems. However, analysis of a dotA mutant of L. longbeachae showed that the Dot/Icm type IV secretion system is also essential for the virulence of L. longbeachae. In contrast to L. pneumophila, L. longbeachae does not encode flagella, thereby providing a possible explanation for differences in mouse susceptibility to infection between the two pathogens. Furthermore, genome analysis and electron microscopy suggested that L. longbeachae is encapsulated. These species-specific differences may account for the different environmental niches and disease epidemiology.

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 investigated in collaboration with the group of M. Swanson (University Michigan, USA) the LetA/LetS two-component system and the role of the regulatory protein DskA. Analysis of a mutant carrying a threonine substitution at position 311 (T311M) of LetS allowed us to propose that the LetA/LetS system exhibits rheostat activity likely conferring versatility to adapt to fluctuating environments. Furthermore, DksA responds to the level of ppGpp and other stress signals to co-ordinate L. pneumophila differentiation.

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. We have recently shown that L. pneumophila uses one of its F-box encoding genes to manipulate ubiquitination signaling of its host cell.

Keywords: comparative genomics, transcriptome, Legionella, virulence, regulation

Cazalet C, Gomez-Valero L, Rusniok C, Lomma M, Dervins-Ravault D, Newton H.J, Sansom FM Jarraud S, Zidane N, Ma L, Bouchier C, Etienne J, Hartland EL and C. Buchrieser (2010) Analysis of the Legionella longbeachae genome and transcriptome uncovers unique strategies to cause Legionnaires disease. PLoS Genet. 19;6(2):e1000851.

Lomma M, Dervins-Ravault D, Rolando M, Nora T, Newton HJ, Samson FM, Sahr T, Gomez-Valero L, Jules M, Hartland EL and Buchrieser C (2010) The Legionella pneumophila F-box protein AnkB modulates ubiquitination of the host protein parvin B to promote intracellular replication. Cell Microbiology 12(9) :1272-1291

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

Nora T, Lomma M, Gomez-Valero L, Buchrieser C (2009) Molecular mimicry: an important virulence strategy employed by Legionella pneumophila to subvert host functions. Future Microbiol. 4:691-701

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.