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荚膜谱系中的感染特征。

Infection characteristics among capsule lineages.

作者信息

Anderson Mark T, Himpsl Stephanie D, Kingsley Leandra G, Smith Sara N, Bachman Michael A, Mobley Harry L T

机构信息

University of Michigan, Michigan Medicine. Department of Microbiology and Immunology. Ann Arbor, MI U. S. A.

University of Michigan, Michigan Medicine. Department of Pathology. Ann Arbor, MI U. S. A.

出版信息

bioRxiv. 2025 Mar 7:2024.08.23.609398. doi: 10.1101/2024.08.23.609398.

Abstract

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 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, 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 .

摘要

是一种与医疗保健相关的病原体,可引起包括菌血症和肺炎在内的严重感染。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的荚膜位点(KL)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和其他荚膜对感染的作用。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脾脏、肝脏和肾脏的荚膜依赖性定植。在菌血性肺炎模型中也观察到了类似的结果,即所有测试的临床来源菌株在原发性肺部感染部位以及血液传播到次要器官方面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。这些发现共同表明,对巨噬细胞吞噬作用的谱系特异性抗性可能会提高临床适应性的存活率和抗菌防御能力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8aa4/11887697/8754b62fe91b/nihpp-2024.08.23.609398v2-f0001.jpg

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