Microbiota-Associated Biofilm Regulation Leads to Vibrio cholerae Resistance Against Intestinal Environmental Stress.
Microbiota-Associated Biofilm Regulation Leads to Vibrio cholerae Resistance Against Intestinal Environmental Stress.
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DOI：
10.3389/fcimb.2022.861677
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发表时间：
2022
影响因子：
5.7
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中科院分区：
文献类型：
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肠道微生物群中的肠道微生物对宿主防御胃肠道病原体（包括霍乱的病原体--霍乱弧菌）做出了重要贡献。由于个体间微生物群的变化驱动感染易感性的个体差异，我们研究了宿主和霍乱弧菌基因表达在感染不同模型人类肠道群落移植的乳鼠过程中，包括感染易感配置代表霍乱流行地区复发性腹泻和营养不良受损的群落和健康个体的代表性抗感染微生物群特征。与具有抗性微生物群的动物定殖相比，携带用霍乱弧菌攻击的易感微生物群的动物下调与活性氧/氮应激的产生相关的基因，而这些动物中的霍乱弧菌上调生物膜相关基因。我们发现，在易感微生物感染环境中，霍乱弧菌对氧化应激和由肠道微生物作用产生的抑制性胆汁代谢产物更具抵抗力，并且这两种表型都依赖于生物膜相关基因，包括vpsL。我们还表明，易感和抗感染的微生物驱动不同的胆汁酸组成在体内的胆盐水解酶的作用。总之，这些发现提供了更好的理解微生物群如何使用多种机制来调节霍乱弧菌遇到的感染相关宿主环境，导致感染易感性的细菌依赖性差异。
The commensal microbes of the gut microbiota make important contributions to host defense against gastrointestinal pathogens, including Vibrio cholerae, the etiologic agent of cholera. As interindividual microbiota variation drives individual differences in infection susceptibility, we examined both host and V. cholerae gene expression during infection of suckling mice transplanted with different model human commensal communities, including an infection-susceptible configuration representing communities damaged by recurrent diarrhea and malnutrition in cholera endemic areas and a representative infection-resistant microbiota characteristic of healthy individuals. In comparison to colonization of animals with resistant microbiota, animals bearing susceptible microbiota challenged with V. cholerae downregulate genes associated with generation of reactive oxygen/nitrogen stress, while V. cholerae in these animals upregulates biofilm-associated genes. We show that V. cholerae in susceptible microbe infection contexts are more resistant to oxidative stress and inhibitory bile metabolites generated by the action of commensal microbes and that both phenotypes are dependent on biofilm-associated genes, including vpsL. We also show that susceptible and infection-resistant microbes drive different bile acid compositions in vivo by the action of bile salt hydrolase enzymes. Taken together, these findings provide a better understanding of how the microbiota uses multiple mechanisms to modulate the infection-associated host environment encountered by V. cholerae, leading to commensal-dependent differences in infection susceptibility.