Integrative Biology of Emerging Infectious Diseases (IBEID) / Principal investigators
Biology of Intracellular Bacteria Unit
Institut Pasteur 25-28 rue du docteur Roux, 75015 Paris
Research area of the Unit
We investigate and characterize the molecular, genetic and cellular basis of the infection by Legionella. Legionella are environmental bacteria but some species like Legionella pneumophila or Legionella longbeachae are also opportunistic pathogens that cause Legionnaires' disease, a severe pneumonia, in particular in people whose immune defenses are weakened. We aim to understand 1) the relationship between virulence and genetic diversity among different isolates of Legionella pneumophila and different species of Legionella, to decipher 2) the mechanisms leading to this diversity and to understand 3) the role diversity plays in infection and environmental adaptation. In line with this, we aim to gain knowledge on 4) how Legionella adapts/regulates its cycle between a eukaryotic host and the environment and to understand 5) the function newly identified putative virulence factors of Legionella pneumophila and Legionella longbeachae have in the intracellular infection cycle.
Contribution to the programme
Legionella is a privileged model to study evolution of virulence and to understand the emergence of human pathogens from the environment. The co-evolution of Legionella and protozoa has allowed their adaptation to eukaryotic cells. The genus Legionella comprises 53 species but over 95% of Legionnaires’ disease cases are caused by L. pneumophila and L. longbeachae alone. Thus an intriguing question we plan to answer is “What are the genetic specificities of these two Legionella species leading to their predominance in human disease?” By studying the diversity of the genus Legionella we want to i) understand how bacterial pathogens emerge from environmental life styles, ii) identify the underlying evolutionary mechanisms, iii) identify the repertoire of eukaryotic-like proteins of Legionella as these are proven virulence factors subverting host functions during disease and analyze (ii) their evolutionary origin. By combining an in depth phylogenetic and evolutionary analysis with functional studies a deeper understanding of the events and mechanisms that led to the emergence of human pathogenic strains from protozoan parasites should be gained.
References over the past 5 years
1. Sahr T, Rusniok C, Dervins-Ravault D, Sismeiro O, Coppee JY, Buchrieser C (2012) Deep sequencing defines the transcriptional map of L. pneumophila and identifies growth phase-dependent regulated ncRNAs implicated in virulence. RNA Biol. 9(4).
2. Gomez-Valero L, Rusniok C, Jarraud S, Vacherie B, Rouy Z, Barbe V, Medigue C, Etienne J, Buchrieser C. (2011) Extensive recombination events and horizontal gene transfer shaped the Legionella pneumophila genomes. BMC Genomics 12:536
3. Lomma M, Dervins-Ravault D, Rolando M, Nora T, Newton HJ, Sansom FM, Sahr T, Gomez-Valero L, Jules M, Hartland EL, Buchrieser C. (2010) The Legionella pneumophila F-box protein Lpp2082 (AnkB) modulates ubiquitination of the host protein parvin B and promotes intracellular replication. Cell Microbiol 12(9):1272-1291
4. Cazalet C, Gomez-Valero L, Rusniok C, Lomma M, Dervins-Ravault D, Newton HJ, Sansom FM, Jarraud S, Zidane N, Ma L, Bouchier C, Etienne J, Hartland EL, Buchrieser C. (2010) Analysis of the Legionella longbeachae Genome and Transcriptome Uncovers Unique Strategies to Cause Legionnaires' Disease. PLoS Genet 6(2): e1000851.
5. Albert-Weissenberger C, Sahr T, Sismeiro O, Hacker J, Heuner K, Buchrieser C. (2010) Control of flagellar gene regulation in Legionella pneumophila and its relation to growth phase. J Bacteriol 192(2):446-55.
6. 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.
7. Cazalet C, Jarraud S, Ghavi-Helm Y, Kunst F, Glaser P, Etienne J, Buchrieser C. (2008) Multigenome analysis identifies a worldwide distributed epidemic Legionella pneumophila clone that emerged within a highly diverse species. Genome Res. 18(3):431-41.