A mouse model displays host and bacterial strain differences in Aerococcus urinae urinary tract infection

Abstract

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.

Aerococcus urinae — significance of detection in the paediatric urinary tract: a case series

“…A bladder diverticulum was found in a 5-year-old boy with malodorous urine [ 8 ], and prior pyeloplasty and VUR were described in a 12-year-old boy with an A. urinae UTI [ 10 ]. The association of urogenital disorders and recurrent detection also correlates with data from a mouse model that showed susceptibility to prolonged bacteriuria with A. urinae in mice with inherent vesicoureteral reflux [ 19 ]. Our findings together with the existing literature suggest that A. urinae bacteriuria may indicate an underlying urogenital disorder.…”

Whole‐grain flat rice noodles improve lipid metabolism in high‐fat‐diet‐fed mice in association with gut microbiota

“…It has been confirmed that the abundance of Desulfovibrio in patients with intestinal disease differed significantly from that in the healthy populations (Liu et al., 2020). Aerococcus is associated with inflammation such as urinary tract infection (Gilbert et al., 2021). Corynebacterium is a Gram‐positive bacillus that is mostly a conditional pathogen that can cause various infections such as respiratory infections (Mangutov et al., 2021).…”

Urinary Microbiota Shift is Associated with a Decline in Renal Function in the Aging Kidney

“…Speci cally, Finegoldia magna has been shown to activate human blood-derived neutrophils via CD66b, the neutrophil surface receptor responsible for downstream signaling during in ammation. In addition, Aerococcus urinae, belonging to f_Aerococcaceae, was also altered in the female CF group, correlates positively with renal histological in ammation, neutrophil recruitment and increased pro-in ammatory cytokines, and has been associated with chronic persistent in ammation of the kidneys [22]. Therefore, it can be speculated that renal aging is affected by in ammatory activation, which alters the urinary microbiota, and in turn these changes exacerbate in ammation.…”

“…LEfSe analysis showed enrichment of F_Staphylococcaceae in the CM group compared to the AM group (LDA score > 2.0, P < 0.05). These bacteria have been associated with bladder cancer and urinary tract infections [21,22], suggesting that age-associated changes in the urinary microbiota may make males more susceptible to bladder cancer and other urinary tract diseases (Fig. 4E, F).…”