Pathogenesis of legionella

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Research themes

Legionellosis is a severe community or hospital acquired pneumonia. Despite prevention measures, legionellosis prevalence did not significantly decrease during the last decade. Moreover, in spite of early diagnosis, the mean case mortality rate about 10% of adequately treated community acquired Legionnaires’ disease is considered high and unsatisfactory; Hospital-acquired legionellosis can reach more than 50% of case mortality rate, with immunocompromised persons being more susceptible, and patients with legionnaire’s disease can develop severe sepsis. Thus, legionellosis is still a major medical problem for developed and emerging countries, and yet much needs to develop additional therapeutics to improve the care of the patients.

Legionella pneumophila is the most common causative agent of the severe pneumonia legionellosis. Legionella pathogenic strains emerge from the environment after intracellular multiplication in amoeba, are disseminated by water aerosols technologies, and infect alveolar macrophages of human lungs. L. pneumophila serogroup1 (sg1) is retrieved in 95% of clinical isolates while it represents 28% of environmental Legionella. The prevalence of L. pneumophila sg1 in legionellosis suggests that this strain exhibits more virulence towards humans than other Legionella strains, but virulence determinants are not precisely defined.

The final aim of our project is to understand some aspects of Legionella virulence from molecular mechanisms to clinical microbiology and molecular epidemiology of legionellosis in order to propose, in a long term, new therapeutic and prophylactic approaches. The team gathers complementary skills, from molecular aspects of the Legionella-host cells relationship (molecular microbiology, cellular biology of amoeba, macrophages, pneumocytes, and bacterial-host cell proteins interactions) to physio/immuno-pathology on mouse model, and human infection (molecular epidemiology of human legionellosis). It is closely linked with the National Reference Centre for Legionella located in Lyon whose its head, Dr. S. Jarraud, is the co-PI of the research group.

Main achievements

– Identification of TolC protein as a major player of multi-drug resistance and virulence in Legionella pneumophila (2007-2009)
– Identification of a two-component sensor kinase that controls the bifunctional diguanylate cyclase-phosphodiesterase Lpl0329 to modulate c-diGMP synthesis (2009-2011).
– Characterisation of the protein kinase LegK2 as a type IV secretion system effector involved in endoplasmic reticulum recruitment and intracellular replication of Legionella pneumophila (2009-2011).
– Demonstration that L. pneumophila-infected microglial cells restrict bacterial growth by activating the inflammasome pathway following flagellin detection (2010-2012)

Sponsors

INSERM, CNRS, Université Lyon 1, ANSES, ANR, Programme Avenir Lyon Saint-Etienne (ANR-11-IDEX-0007) of Université de Lyon, within the program “Investissements d’Avenir” operated by the French National Research Agency (ANR), LABEX ECOFECT (ANR-11-LABX-0042) of Université de Lyon, within the program “Investissements d’Avenir” (ANR-11-IDEX-0007) operated by the French National Research Agency (ANR), FINOVI

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