Use of probiotics to control Giardia: determination of the molecular mechanism of antiparasitic action
Laboratory: UMR 7245 CNRS-MNHN (Director: Philippe GRELLIER), BAMEE Team (Directors: Coralie MARTIN and Isabelle FLORENT).
Coordinator of the project: Pr. Isabelle FLORENT
Keywords: Giardia duodenalis, giardiosis, Probiotics, Lactobacillus, signaling pathways
Profile and skills: PhD with strong background in microbiology, cellular and molecular biology, imaging. A previous experience in parasitology, transcriptomic and in vivo models will be highly appreciated. A good knowledge of English is expected, communication skills will also be appreciated.
Description of the project:
Giardia duodenalis is the protist responsible for giardiosis, an intestinal disease affecting humans and numerous mammals, causing digestive disorders (diarrhea and maldigestion) in 2 to 7.5% of population in industrialized countries, 12 to 30% in developing countries, and affecting ~ 15.6% of dogs and ~ 10.3% of cats. Infections occur after ingestion of cysts (present in food or contaminated water), that excyst to liberate proliferating trophozoite in the host duodenum, where they cause the symptoms of the disease.
Anti-giardial medications are currently limited, both in human and animals. Aiming at developing novel anti-giardial approaches, we have recently discovered and patented (Bermudez-Humaran et al., 2016) a new therapeutic track, based on the protective action (in vitro and in vivo in a mouse model of giardiosis as well as in a clinical trial in puppies), provided by probiotic lactobacilli strains thanks to the action of their bile salts hydrolases (BSHs) enzymes. These BSH enzymes metabolize the conjugated bile salts (that are non-toxic for Giardia) into deconjugated bile salts which are toxic for the parasite. However, the mechanism of action on parasites of these deconjugated bile salts and BSHs of these lactobacilli remain unknown and is the subject of the current project.
These will be first explored in vitro, on parasite culture, using deconjugated bile salts, recombinant forms of BSHs (available in the laboratory) and supernatants of selected lactobacilli (also available), based on our
recent publications (Travers et al., 2016; Allain et al., 2018a, 2018b), and imaging approaches. Cellular and ultrastructural damages will be assayed using electron microscopy (SEM, TEM), immunofluorescence and cytometry; an RNAseq comparative study (treated versus control parasites) will be undertaken to identify impacted genes and metabolic pathways (up and down regulated). Then, a widening of the effects will be done on additional Giardia strains as well as using in vivo models of giardiosis as described (Allain et al., 2018a, 2018b). This project takes part in a long term consortium implying two other Île-de-France partners, INRA-MICALIS Eq Probihôte (Dr. L. Bermudez & co) and UMR BIPAR INRA-ENVA-ANSES Eq PARALIM (Dr. B. Polack & collaborators).
Funding: Région Île-de-France (DIM1HEALTH) for 2 years. The post-doc is expected to start between Oct. 2018 and January 2019.
Salary: ~2000 €/month (net pay).
How to apply: Send until August 31st 2018, a CV, a motivation letter and the name and contact information of 3 references to Prof. Isabelle FLORENT (firstname.lastname@example.org).
-Allain T, Chaouch S, Thomas M, Vallée I, Buret AG, Langella P, Grellier P, Polack B, Bermúdez-Humarán LG*, Florent I*. Bile-Salt- Hydrolases from the probiotic strain Lactobacillus johnsonii La1 mediate anti-giardial activity in vitro and in vivo. Frontiers in Microbiology (2018), 8, 2707.
-Allain T, Chaouch S, Thomas M, Travers MA, Vallée I, Langella P, Grellier P, Polack B, Florent I*, Bermúdez-Humarán LG*. Bile Salt Hydrolase Activities: A Novel Target to Screen Anti-Giardia Lactobacilli? Frontiers in Microbiology (2018), 9, 89.
-Bermudez-Humaran, L.G., Allain, T., Florent, I., Langella, P., Grellier, P., Travers, M.-A., Polack, B., 2016. Compositions for the Inhibition of Giardia lamblia. Brevet: WO2016020544 (A1).
-Travers MA, Sow C, Zirah S, Deregnaucourt C, Chaouch S, Queiroz RM, Charneau S, Allain T, Florent I, Grellier P. 2016. Deconjugated bile salts produced by extracellular bile-salt hydrolase-like activities from the probiotic Lactobacillus johnsonii La1 inhibit Giardia duodenalis in vitro growth, Frontiers in Microbiology; 7:1453