Cellular biology of bacterial infections- March 2020 CFATG
Cellular biology of bacterial infections- March 2020

Team: Cell Biology of Bacterial Infections

Institut de Recherche en Infectiologie de Montpellier (IRIM) CNRS UMR9004
1919 route de Mende
34293 Montpellier
France
Tel : +33 4 34 35 94 59
Fax : +33 4 34 35 94 14

Team presentation

http://www.irim.cnrs.fr/index.php/en/researchh/teams/cellular-biology-of-bacterial-infections

Team leader : : Dr Matteo Bonazzi, DR2 CNRS, matteo.bonazzi@irim.cnrs.fr

Team members, 2020 :

Arthur Bienvenu (Master)
Mélanie Burette (PhD)
Franck Cantet (Engineer, CNRS)
Maud Laffitte (Master)
Amélie Machura (Technician)
Eric Martinez (Research Associate, CNRS) eric.martinez@irim.cnrs.fr


From left to right : Eric Martinez, Amélie Machura, Franck Cantet, Mélanie Burette, Matteo Bonazzi, Angélique Perret (Master, 2019)

Keywords: Coxiella burnetii, host/pathogen interactions, autophagy, intracellular trafficking, high-throughput screening, cellular microbiology

Research focus
Our research focuses on the characterization of the infectious cycle of Coxiella burnetii, the bacterium responsible for Q fever, an incapacitating human disease in its acute form which can become fatal in its chronic form. This bacterium is most often transmitted by air between contaminated farms and humans, causing epidemics with serious economic and health consequences. Our laboratory, established in 2011 in Montpellier, has developed a high-throughput screening method to identify the virulence factors of this bacterium. Thus, we will be able to determine how the bacteria enter human cells and which genes are involved in its development. During infection, this intracellular bacterium generates a parasitophorous vacuole with autolysosomal properties, called Coxiella-Containing Vacuole (CCV), by using effector proteins that divert the vesicular traffic pathways (Figure 1).

Figure 1. Infectious cycle of Coxiella burnetii. This intracellular bacterium mainly develops in animal reservoirs and infects humans in an airborne manner. 40 % of contaminated individuals develop Q Fever, in 2 % of the cases, the disease progresses to a chronic form. Once internalised by cells, the bacterium resides in endosomes that mature in the degradative pathway. The drop in pH in these endosomes activates the bacterium metabolism. The latter secretes effector proteins (CvpA-F) that will divert the intracellular trafficking to generate a parasitophorous vacuole (CCV) in which the bacterium multiplies in high numbers. Adapted from « Burette and Bonazzi, Cellular Microbiology, in press ».

Autophagy has been shown to promote the development of CCVs and bacterial effector proteins can manipulate the processes of autophagy. Among these proteins, we have demonstrated that CvpB participates in the increase of phosphatidylinositol 3-phosphate (PI3P) on the surface of CCVs, a critical event for the homotypic and heterotypic fusion of CCVs (Martinez et al., 2016) and that CvpF promotes the anchoring of LC3B-II to CCVs via an interaction with the RAB GTPase RAB26 (Siadous et al., 2020). Importantly, these two proteins play a major role in the virulence of Coxiella burnetii in vivo. The approaches developed in our laboratory allow us to understand how Coxiella manipulates cellular mechanisms, such as autophagy, to establish a replicative niche and develop in cells. Ultimately, a better understanding of the Coxiella burnetii infectious cycle will allow the development of anti-infectious molecules targeting both infected cells and the pathogen.

Key publications:

1. Siadous F., Cantet F., Van Schaik E.J., Burette M., Allombert J., Lakhani A., Samuel J., Bonazzi M.# and Martinez E.# (2020) Coxiella effector protein CvpF subverts Rab26-dependent autophagy to promote vacuole biogenesis and virulence. Autophagy, in press.

2. Martinez E., Allombert J., Cantet F., Lakhani A., Yandrapalli N., Neyret A., Norville I., Favard C., Muriaux D. and Bonazzi M. (2016) Coxiella burnetii effector CvpB modulates phosphoinositide metabolism for optimal vacuole development. PNAS, 113(23):E3260-9.

3. Martinez E., Cantet F., Fava L., Norville I. and Bonazzi M. (2014) Identification of OmpA, a Coxiella burnetii protein involved in host cell invasion, by multi-phenotypic high-content screening. PloS Pathogens, 10 (3) e1004013.

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