Host-pathogen interactions and resilience
Group leader: Dominique FERRANDON



I – Toxin and xenobiotics-inuced purge and subsequent recovery of enterocytes


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The intestine is a critical interface with the environment. By feeding, animals get exposed to toxins or toxicants contaminating nutrients.

We have discovered a novel stress response of Drosophila enterocytes: pore-forming toxin or xenobiotics trigger a limited extrusion of apical cytoplasm and damaged organelles, possibly along with the toxicant, thus yielding a homogenously thin intestinal epithelium. There is no increased enterocyte cell death in the process.

The enterocytes then recover their original shape and volume in 6-9 hours by a noncell-autonomous process. This response protects enterocytes from occasional intoxications from microbial or environmental origin present in contaminated food. This protective response thus involves two distinct phases. First occurs a limited extrusion of cytoplasm that does not lyse it, the purge; next, a recovery phase takes place allowing the intestinal epithelium to regain its original thickness and morphology. We showed that this mechanism is conserved in Mammals. This work has been published in Cell Host and Microbe (see also the Preview).



Above, two videos of the cytoplasmic purge on the  human epithelial cell line Caco-2 (basal membrane to the top, apical to the bottom). 



In vivo cytoplasmic purge on Drosophila intestinal cells (basal membrane to the bottom).



We also study the host-pathogen interactions from the pathogen side in collaboration with microbiologists working on Serratia marcescens, in Eleonora Garcia Vescovi lab (Argentina).


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II – Pseudomonas aeruginosa virulence systems analysis in Drosophila


Pseudomonas aeruginosa is an opportunistic Human pathogen and the fourth most commonly isolated nosocomial pathogen. Even though P. aeruginosa infections are mostly curable, an acute fulminant infection like pneumonia, burn wound infection or sepsis, leads to a very strong mortality rate. We analyse the role of some virulence factors in their function to circumvent the Drosophila cellular immune response. This work in done in collaboration with Fred Ausubel lab (Boston, USA). We recently published an article on the role of an opsonin (Tep4) in P. aeruginosa PA14 phagocytosis. Unexpectedly, we showed that the bacterial factor RhlR can inhibit this opsonization independently from other quorum sensing molecules, although RhlR is part of the quorum sensing system (EMBO Rep. 2018 May;19(5).) (link on the article). This work shows that in vivo models of infection allow the observation of functions that are undetectable in vitro. This RhlR function would be conserved during mammalian infections.




III – Host-pathogen interactions with the microsporidia Tubulinosema ratisbonensis


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Microsporidia are intracellular parasites that affect honey bees. We showed the importance of host lipid metabolism for the parasitic proliferation in a Drosophila model of infection. This work is done in collaboration with Frédéric Delbac lab (Clermont-Ferrand, France), working on parasites and honey bees.

Our recently published genetic dissection of host lipid metabolism identifies a crucial compound hijacked by T.  ratisbonensis: phosphatidic acid (Nat Microbiol. 2019 Apr;4(4):645-655) (link to the article).