Becknell Brian, Mohamed Ahmad Z, Li Birong, Wilhide Michael E, Ingraham Susan E
Nephrology Section, Nationwide Children's Hospital, Columbus, OH, United States of America; Department of Pediatrics, Ohio State University School of Medicine, Columbus, OH, United States of America; Center for Clinical and Translational Research, The Research Institute at Nationwide Children's, Columbus, OH, United States of America.
Department of Urology, University of Louisville, Louisville, KY, United States of America.
PLoS One. 2015 Sep 24;10(9):e0139077. doi: 10.1371/journal.pone.0139077. eCollection 2015.
Urinary stasis is a risk factor for recurrent urinary tract infection (UTI). Homozygous mutant Megabladder (Mgb-/-) mice exhibit incomplete bladder emptying as a consequence of congenital detrusor aplasia. We hypothesize that this predisposes Mgb-/- mice to spontaneous and experimental UTI.
Mgb-/-, Mgb+/-, and wild-type female mice underwent serial ultrasound and urine cultures at 4, 6, and 8 weeks to detect spontaneous UTI. Urine bacterial isolates were analyzed by Gram stain and speciated. Bladder stones were analyzed by x-ray diffractometry. Bladders and kidneys were subject to histologic analysis. The pathogenicity of coagulase-negative Staphylococcus (CONS) isolated from Mgb-/- urine was tested by transurethral administration to culture-negative Mgb-/- or wild-type animals. The contribution of urinary stasis to CONS susceptibility was evaluated by cutaneous vesicostomy in Mgb-/- mice.
Mgb-/- mice develop spontaneous bacteriuria (42%) and struvite bladder stones (31%) by 8 weeks, findings absent in Mgb+/- and wild-type controls. CONS was cultured as a solitary isolate from Mgb-/- bladder stones. Bladders and kidneys from mice with struvite stones exhibit mucosal injury, inflammation, and fibrosis. These pathologic features of cystitis and pyelonephritis are replicated by transurethral inoculation of CONS in culture-negative Mgb-/- females, whereas wild-type animals are less susceptible to CONS colonization and organ injury. Cutaneous vesicostomy prior to CONS inoculation significantly reduces the quantity of CONS recovered from Mgb-/- urine, bladders, and kidneys.
CONS is an opportunistic uropathogen in the setting of urinary stasis, leading to enhanced UTI incidence and severity in Mgb-/- mice.
尿潴留是复发性尿路感染（UTI）的一个危险因素。纯合突变的巨膀胱（Mgb-/-）小鼠由于先天性逼尿肌发育不全而出现膀胱排空不完全。我们假设这使Mgb-/-小鼠易发生自发性和实验性UTI。
对Mgb-/-、Mgb+/-和野生型雌性小鼠在4周、6周和8周时进行系列超声检查和尿培养，以检测自发性UTI。对尿液细菌分离株进行革兰氏染色和鉴定。通过X射线衍射分析膀胱结石。对膀胱和肾脏进行组织学分析。通过经尿道给药将从Mgb-/-尿液中分离出的凝固酶阴性葡萄球菌（CONS）接种到培养阴性的Mgb-/-或野生型动物体内，测试其致病性。通过对Mgb-/-小鼠进行皮肤膀胱造口术评估尿潴留对CONS易感性的影响。
到8周时，Mgb-/-小鼠出现自发性菌尿（42%）和鸟粪石膀胱结石（31%），而Mgb+/-和野生型对照中未出现这些情况。CONS作为从Mgb-/-膀胱结石中分离出的唯一菌株被培养出来。患有鸟粪石结石的小鼠的膀胱和肾脏表现出黏膜损伤、炎症和纤维化。经尿道接种CONS可在培养阴性的Mgb-/-雌性小鼠中复制膀胱炎和肾盂肾炎的这些病理特征，而野生型动物对CONS定植和器官损伤的易感性较低。在接种CONS之前进行皮肤膀胱造口术可显著减少从Mgb-/-尿液、膀胱和肾脏中回收的CONS数量。
在尿潴留情况下，CONS是一种机会性尿路病原体，导致Mgb-/-小鼠的UTI发病率和严重程度增加。
