Lebrun-Corbin Marine, Cheung Bettina H, Hullahalli Karthik, Dailey Katherine G, 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, Illinois, USA.
Division of Infectious Disease, Brigham and Women's Hospital, Boston, Massachusetts, USA.
mBio. 2025 May 14;16(5):e0313624. doi: 10.1128/mbio.03136-24. Epub 2025 Apr 10.
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 cecum expanded rapidly. Hence, the stomach constitutes a significant barrier against gastrointestinal carriage of which may have clinical implications for hospitalized patients.
While is rarely part of the normal human microbiome, carriage of the bacterium is quite frequent in hospitalized patients and residents of long-term care facilities. carriage is a precursor to infection. Options for treating infections caused by difficult-to-treat strains are dwindling, underscoring the urgency to better understand and impede pre-infection stages, such as colonization. Here, we use vancomycin-treated mice to model antibiotic-treated patients who become colonized with in their gastrointestinal tracts. We identify the stomach as a major barrier to the establishment of gastrointestinal carriage. These findings suggest that efforts to prevent gastrointestinal colonization should focus not only on judicious use of antibiotics but also on investigation into how the stomach eliminates orally ingested .
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，该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[具体物质未提及]。多个临床分离株均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，该模型确实代表了携带而非感染。然后，我们使用条形码[具体物质未提及]文库以及基于序列标签的微生物群体分析（STAMPR）分析流程，以量化胃肠道携带建立过程中的细菌群体动态和瓶颈。分析表明，大多数[具体细菌未提及]群体在胃中迅速被清除，但少数进入小肠和盲肠的细菌迅速繁殖。因此，胃构成了[具体细菌未提及]胃肠道携带的重要屏障，这可能对住院患者具有临床意义。
虽然[具体细菌未提及]很少是正常人类微生物群的一部分，但在住院患者和长期护理机构的居民中，该细菌的携带情况相当常见。[具体细菌未提及]携带是感染的先兆。治疗由难治疗的[具体细菌未提及]菌株引起的感染的选择正在减少，这凸显了更好地理解和阻碍感染前阶段（如定植）的紧迫性。在此，我们使用万古霉素处理的小鼠来模拟在胃肠道中定植了[具体细菌未提及]的抗生素治疗患者。我们确定胃是建立胃肠道携带的主要屏障。这些发现表明，预防胃肠道定植的努力不仅应集中在合理使用抗生素上，还应调查胃如何清除口服摄入的[具体细菌未提及]。
