Department of Cell Biology and Molecular Genetics, University of Maryland at College Park, College Park, MD 20742.
Center for Bioinformatics and Computational Biology, University of Maryland at College Park, College Park, MD 20742.
Proc Natl Acad Sci U S A. 2022 Dec 13;119(50):e2209383119. doi: 10.1073/pnas.2209383119. Epub 2022 Dec 5.
Healthcare-associated infections are major causes of complications that lead to extended hospital stays and significant medical costs. The use of medical devices, including catheters, increases the risk of bacterial colonization and infection through the presence of a foreign surface. Two outcomes are observed for catheterized patients: catheter-associated asymptomatic bacteriuria and catheter-associated urinary tract infection (CAUTI). However, the relationship between these two events remains unclear. To understand this relationship, we studied a murine model of CAUTI. In this model, we also observe two outcomes in infected animals: acute symptoms that is associated with CAUTI and chronic colonization that is associated with asymptomatic bacteriuria. The timing of the acute outcome takes place in the first week of infection, whereas chronic colonization occurs in the second week of infection. We further showed that mutants lacking genes encoding type III secretion system (T3SS), T3SS effector proteins, T3SS injection pore, or T3SS transcriptional activation all fail to cause acute symptoms of CAUTI. Nonetheless, all mutants defective for T3SS colonized the catheter and bladders at levels similar to the parental strain. In contrast, through induction of the T3SS master regulator ExsA, all infected animals showed acute phenotypes with bacteremia. Our results demonstrated that the acute symptoms, which are analogous to CAUTI, and chronic colonization, which is analogous to asymptomatic bacteriuria, are independent events that require distinct bacterial virulence factors. Experimental delineation of asymptomatic bacteriuria and CAUTI informs different strategies for the treatment and intervention of device-associated infections.
医疗机构相关性感染是导致并发症的主要原因,这些并发症会延长住院时间并带来高昂的医疗费用。医疗器械的使用,包括导管,增加了细菌定植和感染的风险,因为存在外来表面。导管化患者会出现两种结果:导管相关性无症状菌尿症和导管相关性尿路感染(CAUTI)。然而,这两种情况之间的关系尚不清楚。为了了解这种关系,我们研究了 CAUTI 的小鼠模型。在这个模型中,我们还观察到感染动物的两种结果:与 CAUTI 相关的急性症状和与无症状菌尿症相关的慢性定植。急性结果的发生时间在感染的第一周,而慢性定植发生在感染的第二周。我们进一步表明,缺乏编码 III 型分泌系统(T3SS)、T3SS 效应蛋白、T3SS 注射孔或 T3SS 转录激活的基因的突变体都不能引起 CAUTI 的急性症状。尽管如此,所有 T3SS 缺陷的突变体都能以类似于亲本菌株的水平定植导管和膀胱。相比之下,通过诱导 T3SS 主调控因子 ExsA,所有感染动物都表现出急性表型,伴有菌血症。我们的结果表明,类似于 CAUTI 的急性症状和类似于无症状菌尿症的慢性定植是独立的事件,需要不同的细菌毒力因子。对无症状菌尿症和 CAUTI 的实验性描述为器械相关感染的治疗和干预提供了不同的策略。