Lebrun-Corbin Marine, Cheung Bettina H, Hullahalli Karthik, Dailey Katherine, Bailey Keith, Waldor Matthew K, Wunderink Richard G, Bachta Kelly E R, Hauser Alan R
Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Division of Infectious Disease, Brigham and Women's Hospital, Boston, MA, USA.
bioRxiv. 2024 Aug 20:2024.08.19.608679. doi: 10.1101/2024.08.19.608679.
is a common nosocomial pathogen and a major cause of morbidity and mortality in hospitalized patients. Multiple reports highlight that gastrointestinal colonization may precede systemic infections by this pathogen. Gaining a deeper insight into the dynamics of gastrointestinal carriage is an essential step in managing gastrointestinal colonization and could contribute to preventing bacterial transmission and progression to systemic infection. Here, we present a clinically relevant mouse model relying on parenteral vancomycin pretreatment and a single orogastric gavage of a controlled dose of Robust carriage was observed with multiple clinical isolates, and carriage persisted for up to 60 days. Histological and microbiological examination of mice indicated that this model indeed represented carriage and not infection. We then used a barcoded library along with the sequence tag-based analysis of microbial populations (STAMPR) analytic pipeline to quantify bacterial population dynamics and bottlenecks during the establishment of the gastrointestinal carriage. Analysis indicated that most of the population was rapidly eliminated in the stomach, but the few bacteria that moved to the small intestine and the caecum expanded significantly. Hence, the stomach constitutes a significant barrier against gastrointestinal carriage of which may have clinical implications for hospitalized patients.
是一种常见的医院病原体,也是住院患者发病和死亡的主要原因。多项报告强调,这种病原体的胃肠道定植可能先于全身感染。深入了解胃肠道携带的动态变化是管理胃肠道定植的关键步骤,有助于预防细菌传播和发展为全身感染。在此,我们展示了一种临床相关的小鼠模型,该模型依赖于静脉注射万古霉素预处理以及单次经口胃管给予可控剂量的 多个临床分离株观察到了稳定的携带情况,且携带持续长达 60 天。对小鼠的组织学和微生物学检查表明,该模型确实代表携带而非感染。然后,我们使用条形码文库以及基于序列标签的微生物种群分析(STAMPR)分析流程来量化胃肠道携带建立过程中的细菌种群动态和瓶颈。分析表明,大多数 种群在胃中迅速被清除,但少数进入小肠和盲肠的细菌显著扩增。因此,胃构成了对 胃肠道携带的重要屏障,这可能对住院患者具有临床意义。
需注意,原文中存在部分未明确表述的内容(如“a controlled dose of ”“ Robust carriage”等),翻译可能会因信息不完整存在一定局限性。