Vaccine-enhanced competition permits rational bacterial strain replacement in the gut

• 成果类型: Article
• 署名作者: Lentsch, Verena; Woller, Aurore; Rocker, Andrea; Aslani, Selma; Moresi, Claudia; Ruoho, Niina; Larsson, Louise; Fattinger, Stefan A.; Wenner, Nicolas; Barazzone, Elisa Cappio; Hardt, Wolf-Dietrich; Loverdo, Claude; Diard, Mederic; Slack, Emma
• 署名单位: Swiss Federal Institutes of Technology Domain; ETH Zurich; University of Oxford; Sorbonne Universite; Centre National de la Recherche Scientifique (CNRS); Universite Libre de Bruxelles; University of Basel; Swiss Federal Institutes of Technology Domain; ETH Zurich; Uppsala University; University of Oxford
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-9739
• DOI: 10.1126/science.adp5011
• 发表日期: 2025-04-04
• 页码: 74-81
• 关键词: enterica serovar typhimurium; salmonella-typhimurium; escherichia-coli; cooperative virulence; microbiota; colonization; expression; resistance; commensal; vectors

摘要

Colonization of the intestinal lumen precedes invasive infection for a wide range of enteropathogenic and opportunistic pathogenic bacteria. We show that combining oral vaccination with engineered or selected niche-competitor strains permits pathogen exclusion and strain replacement in the mouse gut lumen. This approach can be applied either prophylactically to prevent invasion of nontyphoidal Salmonella strains, or therapeutically to displace an established Escherichia coli. Both intact adaptive immunity and metabolic niche competition are necessary for efficient vaccine-enhanced competition. Our findings imply that mucosal antibodies have evolved to work in the context of gut microbial ecology by influencing the outcome of competition. This has broad implications for the elimination of pathogenic and antibiotic-resistant bacterial reservoirs and for rational microbiota engineering.