Strains used in the studya.

Successful microbial colonization of the gastrointestinal (GI) tract hinges on an organism’s ability to overcome the intense competition for nutrients in the gut between the host and the resident gut microbiome. Enteric pathogens can exploit ethanolamine (EA) in the gut to bypass nutrient competition. However, Klebsiella pneumoniae (K. pneumoniae) is an asymptomatic gut colonizer and, unlike well-studied enteric pathogens, harbors two genetically distinct ethanolamine utilization (eut) loci. Our investigation uncovered unique roles for each eut locus depending on EA utilization as a carbon or nitrogen source. Murine gut colonization studies demonstrated the necessity of both eut loci in the presence of intact gut microbiota for robust GI colonization by K. pneumoniae. Additionally, while some Escherichia coli gut isolates could metabolize EA, other commensals were incapable, suggesting that EA metabolism likely provides K. pneumoniae a selective advantage in gut colonization. Molecular and bioinformatic analyses unveiled the conservation of two eut loci among K. pneumoniae and a subset of the related taxa in the K. pneumoniae species complex, with the NtrC-RpoN regulatory cascade playing a pivotal role in regulation. These findings identify EA metabolism as a critical driver of K. pneumoniae niche establishment in the gut and propose microbial metabolism as a potential therapeutic avenue to combat K. pneumoniae infections.胃肠道（gastrointestinal tract，GI）的成功微生物定植，核心取决于生物体能否克服宿主与肠道常驻微生物组之间的激烈营养竞争。肠致病菌可利用肠道内的乙醇胺（ethanolamine，EA）规避此类营养竞争。然而，肺炎克雷伯菌（Klebsiella pneumoniae，K. pneumoniae）作为一种无症状肠道定植菌，与研究较为深入的肠致病菌不同，其携带有两个遗传特征迥异的乙醇胺利用（ethanolamine utilization，eut）基因座。本研究揭示，两个eut基因座各自具备独特功能，其功能分工取决于乙醇胺是被用作碳源还是氮源。小鼠肠道定植实验证实，在肠道菌群完整的环境中，两个eut基因座均为肺炎克雷伯菌实现高效胃肠道定植所必需。此外，尽管部分肠道分离的大肠杆菌（Escherichia coli）可代谢乙醇胺，但其他共生菌却无法完成该代谢过程，这提示乙醇胺代谢或可为肺炎克雷伯菌的肠道定植提供选择优势。分子与生物信息学分析显示，肺炎克雷伯菌及其物种复合体中的部分相关类群均保留了两个eut基因座，且NtrC-RpoN调控级联在其调控过程中发挥关键作用。本研究结果证实，乙醇胺代谢是肺炎克雷伯菌在肠道中建立生态位的关键驱动因素，并提出靶向微生物代谢或可成为对抗肺炎克雷伯菌感染的潜在治疗策略。