Isolation of derivatives from the food-grade probiotic <i>Lactobacillus johnsonii</i> CNCM I-4884 with enhanced anti-Giardia activity
2025
Boucard, Anne-Sophie | Kulakauskas, Saulius | Alazzaz, Jana | Chaouch, Soraya | Mammeri, Mohamed | Millan-Oropeza, Aaron | Machado, Carine | Henry, Céline | Péchoux, Christine | Richly, Holger | Gassel, Michael | Langella, Philippe | Polack, Bruno | Florent, Isabelle | Bermúdez-Humarán, Luis | MICrobiologie de l'ALImentation au Service de la Santé (MICALIS) ; AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE) | Molécules de Communication et Adaptation des Micro-organismes (MCAM) ; Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS) | Sorbonne Université (SU) | Biologie moléculaire et immunologie parasitaires et fongiques (BIPAR) ; École nationale vétérinaire d'Alfort (ENVA)-Laboratoire de santé animale, sites de Maisons-Alfort et de Normandie ; Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE) | Génétique Animale et Biologie Intégrative (GABI) ; AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE) | Boehringer Ingelheim International GmbH | ANRT 2019/0369 | Boehringer Ingelheim | ANR-23-CE18-0022,BileBaG,Biothérapies à base d'hydrolases de sels biliaires (BSH) pour lutter contre la giardiase(2023)
International audience
显示更多 [+] 显示较少 [-]英语. Giardiasis, a widespread intestinal parasitosis affecting humans and animals, is a growing concern due to the emergence of drug-resistant strains of G. intestinalis. Probiotics offer a promising alternative for preventing and treating giardiasis. Recent studies have shown that the probiotic Lactobacillus johnsonii CNCM I-4884 inhibits G. intestinalis growth both in vitro and in vivo. This protective effect is largely mediated by bile salt hydrolase (BSH) enzymes, which convert conjugated bile acids (BAs) into free forms that are toxic to the parasite. The objective of this study was to use adaptive evolution to develop stress-resistant derivatives of L. johnsonii CNCM I-4884, with the aim of improving its anti-Giardia activity. Twelve derivatives with enhanced resistance to BAs and reduced autolysis were generated. Among them, derivative M11 exhibited the highest in vitro anti-Giardia effect with enhanced BSH activity. Genomic and proteomic analyses of M11 revealed two SNPs and the upregulation of the global stress response by SigB, which likely contributed to its increased BAs resistance and BSH overproduction. Finally, the anti-Giardia efficacy of M11 was validated in a murine model of giardiasis. In conclusion, our results demonstrate that adaptive evolution is an effective strategy to generate robust food-grade bacteria with improved health benefits.
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