Anderson Mark T, Himpsl Stephanie D, Kingsley Leandra G, Smith Sara N, Bachman Michael A, Mobley Harry L T
Department of Microbiology and Immunology, University of Michigan, Michigan Medicine, Ann Arbor, Michigan, USA.
Department of Pathology, University of Michigan, Michigan Medicine, Ann Arbor, Michigan, USA.
mBio. 2025 May 14;16(5):e0055925. doi: 10.1128/mbio.00559-25. Epub 2025 Apr 16.
is a healthcare-associated pathogen that can cause severe infections, including bacteremia and pneumonia. The capsule polysaccharide of is a bacteremia fitness determinant, and previous work defined capsule locus (KL) diversity within the species. Strains belonging to KL1 and KL2 capsule clades produce sialylated polysaccharides and represent the largest subpopulation of isolates from clinical origin. In this study, the contribution of these and other capsules to infection was determined in animal and cellular models. Using a murine model of primary bacteremia, clinical isolates of multiple KL types demonstrated capsule-dependent colonization of the spleen, liver, and kidney following tail vein inoculation. Similar results were observed using a bacteremic pneumonia model, in that all tested strains of clinical origin demonstrated a requirement for capsule in both the primary lung infection site and for bloodstream dissemination to secondary organs. Finally, the capsule from each KL clade was examined for the ability to resist internalization by bone marrow-derived macrophages. Only the sialylated KL1 and KL2 clade strains exhibited capsule-dependent inhibition of internalization, including KL2 capsule produced in a heterologous background. Together, these findings indicate that lineage-specific resistance to macrophage phagocytosis may enhance survival and antibacterial defenses of clinically adapted .
Bacteremia occurs when the host immune system fails to contain bacterial bloodstream replication following an initial inoculation event from either an internal or external source. Capsule polysaccharides play a protective role for during bacteremia, but there is abundant genetic diversity at the capsule-encoding locus within the species. This study compares the infection characteristics of isolates belonging to five capsule types and defines the contributions to infection fitness for each. By characterizing the differences in capsule dependence and infection potential between strains, efforts to combat these life-threatening infections can be focused toward identifying strategies that target the most critical genetic lineages of this important opportunistic pathogen.
是一种与医疗保健相关的病原体，可引起严重感染，包括菌血症和肺炎。[病原体名称]的荚膜多糖是菌血症适应性决定因素，先前的研究确定了该物种内荚膜基因座（KL）的多样性。属于KL1和KL2荚膜分支的菌株产生唾液酸化多糖，是临床来源分离株中最大的亚群。在本研究中，在动物和细胞模型中确定了这些以及其他[病原体名称]荚膜对感染的作用。使用原发性菌血症小鼠模型，多种KL类型的临床分离株在尾静脉接种后显示出荚膜依赖性的脾脏、肝脏和肾脏定植。使用菌血症性肺炎模型观察到类似结果，即所有测试的临床来源菌株在原发性肺部感染部位以及向继发性器官的血流传播中都显示出对荚膜的需求。最后，检测了每个KL分支的荚膜抵抗骨髓来源巨噬细胞内化的能力。只有唾液酸化的KL1和KL2分支菌株表现出荚膜依赖性的内化抑制，包括在异源背景下产生的KL2荚膜。总之，这些发现表明，对巨噬细胞吞噬作用的谱系特异性抗性可能增强临床适应性[病原体名称]的存活和抗菌防御能力。
当宿主免疫系统无法抑制来自内部或外部来源的初始接种事件后细菌在血流中的复制时，就会发生菌血症。荚膜多糖在菌血症期间对[病原体名称]起保护作用，但该物种内荚膜编码基因座存在丰富的遗传多样性。本研究比较了属于五种荚膜类型的[病原体名称]分离株的感染特征，并确定了每种类型对感染适应性的贡献。通过表征[病原体名称]菌株之间荚膜依赖性和感染潜力的差异，对抗这些危及生命的感染的努力可以集中在确定针对这种重要机会性病原体最关键遗传谱系的策略上。
