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

Abstract

<i>Giardia duodenalis</i> (syn. <i>G. lamblia, G. intestinalis</i>) 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), <i>Giardia</i> excysts in the upper intestinal tract to release replicating trophozoites that are responsible for the production of symptoms. In the gut, <i>Giardia</i> cohabits with the host's microbiota, and several studies have revealed the importance of this gut ecosystem and/or some probiotic bacteria in providing protection against <i>G. duodenalis</i> infection through mechanisms that remain incompletely understood. Recent findings suggest that Bile-Salt-Hydrolase (BSH)-like activities from the probiotic strain of <i>Lactobacillus johnsonii</i> La1 may contribute to the anti-giardial activity displayed by this strain. Here, we cloned and expressed each of the three <i>bsh</i> genes present in the <i>L. johnsonii</i> La1 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. <i>In vitro</i> assays 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 against <i>Giardia</i> trophozoites <i>in vitro</i>. 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 strain <i>Lactobacillus johnsonii</i> La1 may yield anti-giardial effects <i>in vitro</i> and <i>in vivo</i>. 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.