Allain Thibault, Chaouch Soraya, Thomas Myriam, Vallée Isabelle, Buret André G, Langella Philippe, Grellier Philippe, Polack Bruno, Bermúdez-Humarán Luis G, Florent Isabelle
Commensal and Probiotics-Host Interactions Laboratory, Micalis Institute, Institut National de la Recherche Agronomique, AgroParisTech, Jouy-en-Josas, France.
UMR7245, Muséum National d'Histoire Naturelle, Centre National de la Recherche Scientifique, Sorbonne-Universités, Paris, France.
Front Microbiol. 2018 Jan 31;8:2707. doi: 10.3389/fmicb.2017.02707. eCollection 2017.
(syn. ) 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), excysts in the upper intestinal tract to release replicating trophozoites that are responsible for the production of symptoms. In the gut, 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 infection through mechanisms that remain incompletely understood. Recent findings suggest that Bile-Salt-Hydrolase (BSH)-like activities from the probiotic strain of La1 may contribute to the anti-giardial activity displayed by this strain. Here, we cloned and expressed each of the three genes present in the 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. 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 trophozoites . 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 La1 may yield anti-giardial effects and . 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.
(同义词)是导致贾第虫病的原生动物寄生虫,贾第虫病是全球最常见且传播最广泛的肠道寄生虫病,可感染人类和动物。摄入包囊(通过受污染的食物或水)后,在肠道上段脱囊释放出负责产生症状的增殖滋养体。在肠道中,与宿主的微生物群共生,多项研究揭示了这种肠道生态系统和/或某些益生菌通过尚未完全了解的机制提供抗感染保护的重要性。最近的研究结果表明,益生菌菌株La1的胆汁盐水解酶(BSH)样活性可能有助于该菌株表现出的抗贾第虫活性。在此,我们克隆并表达了La1基因组中存在的三个基因中的每一个,以研究它们的酶学和生物学特性。虽然BSH47和BSH56表达为重组活性酶,但未检测到BSH12有明显的酶活性。分析允许确定BSH47和BSH56的底物特异性,它们是不同的。这些BSH的建模表明,尽管它们的一级结构保守性较低,但其三维结构具有很强的保守性。两种重组酶都能够介导针对滋养体的抗贾第虫生物学活性。此外,在贾第虫病小鼠模型中测试时,BSH47发挥了显著的抗贾第虫作用。这些结果为来自益生菌菌株La1的活性BSH可能产生抗贾第虫作用的机制提供了新的线索。这些发现为治疗这种广泛传播但被忽视的传染病在人类和兽医学中开辟了新的途径。