A mouse model displays host and bacterial strain differences in Aerococcus urinae urinary tract infection.
A mouse model displays host and bacterial strain differences in Aerococcus urinae urinary tract infection.
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DOI：
10.1242/bio.058931
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发表时间：
2021-08-15
期刊：
影响因子：
2.4
通讯作者：
Wolfe AJ
中科院分区：
文献类型：
--
作者：
Gilbert NM;Choi B;Du J;Collins C;Lewis AL;Putonti C;Wolfe AJ
近年来，尿气球菌的临床意义日益被人们所认识。男性和女性患者，从儿童到老年人，都与尿路感染(尿路感染；急性膀胱炎和肾盂肾炎)有关。尿气球菌也可以是侵入性的，导致尿毒症、心内膜炎和肌肉骨骼感染。尿路假单胞菌感染的发病机制尚不清楚，这主要是由于缺乏动物模型系统。为了应对这一缺口，我们建立了一种小鼠尿路沙门氏菌感染模型。我们比较了雌性C3H/HEN和C57BL/6小鼠的尿路感染情况，并比较了从尿路感染、急迫性尿失禁和膀胱过度活动患者中分离出的四种临床分离株。我们的数据表明，宿主遗传背景对尿路假单胞菌的UTI有调节作用。雌性C57BL/6雌性小鼠迅速清除感染。雌性C3H/HEN小鼠有固有的膀胱输尿管反流，将尿液从膀胱冲到肾脏，容易出现长期的细菌尿。这一结果与尿路假单胞菌感染最常发生在潜在的尿路异常或使他们容易受到细菌感染的疾病的患者中的事实一致。与导致C3H/HEN小鼠膀胱和肾脏感染和炎症的尿路病原体不同，尿路假单胞菌表现出对肾脏的趋向性，即使在将细菌从膀胱中清除后，它也会在肾脏组织中存活。来自不同基因分支的尿气球菌菌株表现出不同的倾向，导致持续性肾脏感染。尿酸气球菌感染的肾脏表现为组织学炎症、中性粒细胞募集和促炎细胞因子增加。这些结果为未来研究尿路假单胞菌和尿路之间的宿主-病原体相互作用奠定了基础。摘要：尿路气球菌属的临床分离株在遗传上是多样化的，并且在小鼠模型中表现出不同的能力来引起尿路感染。感染从膀胱迅速清除，但持续存在，并导致肾脏发炎。
In recent years, the clinical significance of Aerococcus urinae has been increasingly recognized. A. urinae has been implicated in cases of urinary tract infection (UTI; acute cystitis and pyelonephritis) in both male and female patients, ranging from children to older adults. Aerococcus urinae can also be invasive, causing urosepsis, endocarditis, and musculoskeletal infections. Mechanisms of pathogenesis in A. urinae infections are poorly understood, largely due to the lack of an animal model system. In response to this gap, we developed a model of A. urinae urinary tract infection in mice. We compared A. urinae UTI in female C3H/HeN and C57BL/6 mice and compared four clinical isolates of A. urinae isolated from patients with UTI, urgency urinary incontinence, and overactive bladder. Our data demonstrate that host genetic background modulates A. urinae UTI. Female C57BL/6 female mice rapidly cleared the infection. Female C3H/HeN mice, which have inherent vesicoureteral reflux that flushes urine from the bladder up into the kidneys, were susceptible to prolonged bacteriuria. This result is consistent with the fact that A. urinae infections most frequently occur in patients with underlying urinary tract abnormalities or disorders that make them susceptible to bacterial infection. Unlike uropathogens such as E. coli, which cause infection and inflammation both of the bladder and kidneys in C3H/HeN mice, A. urinae displayed tropism for the kidney, persisting in kidney tissue even after clearance of bacteria from the bladder. Aerococcus urinae strains from different genetic clades displayed varying propensities to cause persistent kidney infection. Aerococcus urinae infected kidneys displayed histological inflammation, neutrophil recruitment and increased pro-inflammatory cytokines. These results set the stage for future research that interrogates host-pathogen interactions between A. urinae and the urinary tract. Summary:Aerococcus urinae clinical isolates are genetically diverse and display differential capacity to cause UTI in a mouse model. Infection was rapidly cleared from the bladder, but persisted and caused inflammation in the kidney.
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