Dissemination of antibiotic resistance (AR) genes, often on plasmids, leads to antibiotic-resistant bacterial infections, which is a major problem for animal and public health. Bacterial conjugation is the primary route of AR gene transfer in the mammalian gastrointestinal tract. Significant gaps in knowledge about which gastrointestinal communities and host factors promote plasmid transfer remain. Here, we used Salmonella enterica serovar Kentucky strain CVM29188 carrying plasmid pCVM29188_146 (harboring streptomycin and tetracycline resistance genes) to assess plasmid transfer to Escherichia coli under in vitro conditions and in various mouse strains with a conventional or defined microbiota. As an initial test, the transfer of pCVM29188_146 to the E. coli strains was confirmed in vitro Colonization resistance and, therefore, a lack of plasmid transfer were found in wild-type mice harboring a conventional microbiota. Thus, mice harboring the altered Schaedler flora (ASF), or ASF mice, were used to probe for host factors in the context of a defined microbiota. To assess the influence of inflammation on plasmid transfer, we compared interleukin-10 gene-deficient 129S6/SvEv ASF mice (proinflammatory environment) to wild-type 129S6/SvEv ASF mice and found no difference in transconjugant yields. In contrast, the mouse strain influenced plasmid transfer, as C3H/HeN ASF mice had significantly lower levels of transconjugants than 129S6/SvEv ASF mice. Although gastrointestinal members were identical between the ASF mouse strains, a few differences from C3H/HeN ASF mice were detected, with C3H/HeN ASF mice having significantly lower abundances of ASF members 356 (Clostridium sp.), 492 (Eubacterium plexicaudatum), and 502 (Clostridium sp.) than 129S6/SvEv ASF mice. Overall, we demonstrate that microbiota complexity and mouse genetic background influence in vivo plasmid transfer.IMPORTANCE Antibiotic resistance is a threat to public health. Many clinically relevant antibiotic resistance genes are carried on plasmids that can be transferred to other bacterial members in the gastrointestinal tract. The current study used a murine model to study the transfer of a large antibiotic resistance plasmid from a foodborne Salmonella strain to a gut commensal E. coli strain in the gastrointestinal tract. We found that different mouse genetic backgrounds and a different diversity of microbial communities influenced the level of Escherichia coli that acquired the plasmid in the gastrointestinal tract. This study suggests that the complexity of the microbial community and host genetics influence plasmid transfer from donor to recipient bacteria.

中文翻译：

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小鼠遗传背景影响胃肠道中抗生素抗性质粒的转移。

通常在质粒上传播抗生素抗性（AR）基因会导致抗生素抗性细菌感染，这是动物和公共卫生的主要问题。细菌结合是AR基因在哺乳动物胃肠道中转移的主要途径。关于哪些胃肠道社区和宿主因素促进质粒转移的知识方面的重大差距仍然存在。在这里，我们使用携带质粒pCVM29188_146（携带链霉素和四环素抗性基因）的沙门氏菌肯塔基州血清型CVM29188菌株（体外具有链霉素和四环素抗性基因）来评估质粒在体外条件下以及在具有常规或定义的微生物群的各种小鼠菌株中的转移。作为一项初步测试，证实了pCVM29188_146向大肠杆菌菌株的转移在体外具有抗定殖性，因此，在具有常规微生物群的野生型小鼠中发现缺乏质粒转移。因此，携带改变的舍德勒菌群（ASF）的小鼠或ASF小鼠被用于在确定的微生物群中探查宿主因子。为了评估炎症对质粒转移的影响，我们将白介素10基因缺陷型129S6 / SvEv ASF小鼠（促炎环境）与野生型129S6 / SvEv ASF小鼠进行了比较，发现转导结合体产量无差异。相反，小鼠品系影响质粒转移，因为C3H / HeN ASF小鼠的转导结合体水平明显低于129S6 / SvEv ASF小鼠。尽管ASF小鼠品系之间的胃肠道成员相同，但检测到与C3H / HeN ASF小鼠有一些差异，其中C3H / HeN ASF小鼠的ASF成员356（Clostridium sp。），492（plexeaudaudatum）和502（Clostridium sp。）比129S6 / SvEv ASF小鼠高。总体而言，我们证明了微生物群的复杂性和小鼠遗传背景会影响体内质粒的转移。重要提示抗生素耐药性是对公共健康的威胁。许多临床相关的抗生素抗性基因携带在质粒上，这些质粒可以转移到胃肠道的其他细菌成员中。当前的研究使用鼠模型研究了一种大型抗生素抗性质粒从食源性沙门氏菌菌株到胃肠道肠道共生大肠杆菌菌株的转移。我们发现不同的小鼠遗传背景和不同的微生物群落多样性影响在胃肠道中获得该质粒的大肠杆菌水平。