Holmes Caitlyn L, Dailey Katherine G, Hullahalli Karthik, Wilcox Alexis E, Mason Sophia, Moricz Bridget S, Unverdorben Lavinia V, Balazs George I, Waldor Matthew K, Bachman Michael A
Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA.
Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI, USA.
Nat Commun. 2025 Jan 17;16(1):785. doi: 10.1038/s41467-025-56095-3.
Bacteremia, a leading cause of death, generally arises after bacteria establish infection in a particular tissue and transit to secondary sites. Studying dissemination from primary sites by solely measuring bacterial burdens does not capture the movement of individual clones. By barcoding Klebsiella pneumoniae, a leading cause of bacteremia, we track pathogen dissemination following pneumonia. Variability in organ bacterial burdens is attributable to two distinct dissemination patterns distinguished by the degree of similarity between the lung and systemic sites. In metastatic dissemination, lung bacterial clones undergo heterogeneous expansion and the dominant clones spread to secondary organs, leading to greater similarity between sites. In direct dissemination, bacterial clones exit the lungs without clonal expansion, leading to lower burdens in systemic sites and more dissimilarity from the lung. We uncover bacterial and host factors that influence the dynamics of clonal sharing and expansion. Here, our data reveal unexpected heterogeneity in Klebsiella bacteremia dynamics and define a framework for understanding within-host bacterial dissemination.
菌血症是主要死因之一,通常在细菌在特定组织中建立感染并转移至继发部位后出现。仅通过测量细菌载量来研究原发性部位的播散情况,无法捕捉单个克隆的移动。通过对菌血症的主要致病菌肺炎克雷伯菌进行条形码标记,我们追踪了肺炎后病原体的播散情况。器官细菌载量的差异可归因于两种不同的播散模式,这两种模式以肺部与全身部位之间的相似程度来区分。在转移性播散中,肺部细菌克隆经历异质性扩增,优势克隆扩散至继发器官,导致各部位之间的相似性增加。在直接播散中,细菌克隆未经克隆扩增就离开肺部,导致全身部位的载量较低,且与肺部的差异更大。我们发现了影响克隆共享和扩增动态的细菌和宿主因素。在这里,我们的数据揭示了肺炎克雷伯菌菌血症动态中意想不到的异质性,并定义了一个理解宿主内细菌播散的框架。