Bile-Salt-Hydrolases from the Probiotic Strain Lactobacillus johnsonii La1 Mediate Anti-giardial Activity in Vitro and in Vivo

Thibault Allain, Soraya Chaouch, Myriam Thomas, Isabelle Vallée, André G. Buret, Philippe Langella, Philippe Grellier, Bruno Polack, Luis G. Bermúdez-Humarán, Isabelle Florent

Giardia duodenalis (syn.G. lamblia, G. intestinalis) is the protozoan parasite responsible for giardiasis, the most common and widely spread intestinal parasitic disease worldwide, affecting both humans and animals. After cysts ingestion (through either contaminated food or water),Giardiaexcysts in the upper intestinal tract to release replicating trophozoites that are responsible for the production of symptoms. In the gut,Giardiacohabits with the host's microbiota, and several studies have revealed the importance of this gut ecosystem and/or some probiotic bacteria in providing protection againstG. duodenalisinfection through mechanisms that remain incompletely understood. Recent findings suggest that Bile-Salt-Hydrolase (BSH)-like activities from the probiotic strain ofLactobacillus johnsoniiLa1 may contribute to the anti-giardial activity displayed by this strain. Here, we cloned and expressed each of the threebshgenes present in theL. johnsoniiLa1 genome to study their enzymatic and biological properties. While BSH47 and BSH56 were expressed as recombinant active enzymes, no significant enzymatic activity was detected with BSH12.In vitroassays allowed determining the substrate specificities of both BSH47 and BSH56, which were different. Modeling of these BSHs indicated a strong conservation of their 3-D structures despite low conservation of their primary structures. Both recombinant enzymes were able to mediate anti-giardial biological activity againstGiardiatrophozoitesin vitro. Moreover, BSH47 exerted significant anti-giardial effects when tested in a murine model of giardiasis. These results shed new light on the mechanism, whereby active BSH derived from the probiotic strainLactobacillus johnsoniiLa1 may yield anti-giardial effectsin vitroandin vivo. These findings pave the way toward novel approaches for the treatment of this widely spread but neglected infectious disease, both in human and in veterinary medicine.