Streptozocin-induced diabetic mouse model of urinary tract infection.
Diabetics have a higher incidence of urinary tract infection (UTI), are infected with a broader range of uropathogens, and more commonly develop serious UTI sequelae than nondiabetics. To better study UTI in the diabetic host, we created and characterized a murine model of diabetic UTI using the pancreatic islet beta-cell toxin streptozocin in C3H/HeN, C3H/HeJ, and C57BL/6 mouse backgrounds. Intraperitoneal injections of streptozocin were used to initiate diabetes in healthy mouse backgrounds, as defined by consecutive blood glucose levels of >250 mg/dl. UTIs caused by uropathogenic Escherichia coli (UTI89), Klebsiella pneumoniae (TOP52 1721), and Enterococcus faecalis (0852) were studied, and diabetic mice were found to be considerably more susceptible to infection. All three uropathogens produced significantly higher bladder and kidney titers than buffer-treated controls. Uropathogens did not have as large an advantage in the Toll-like receptor 4-defective C3H/HeJ diabetic mouse, arguing that the dramatic increase in colonization seen in C3H/HeN diabetic mice may partially be due to diabetic-induced defects in innate immunity. Competition experiments demonstrated that E. coli had a significant advantage over K. pneumoniae in the bladders of healthy mice and less of an advantage in diabetic bladders. In the kidneys, K. pneumoniae outcompeted E. coli in healthy mice but in diabetic mice E. coli outcompeted K. pneumoniae and caused severe pyelonephritis. Diabetic kidneys contained renal tubules laden with communities of E. coli UTI89 bacteria within an extracellular-matrix material. Diabetic mice also had glucosuria, which may enhance bacterial replication in the urinary tract. These data support that this murine diabetic UTI model is consistent with known characteristics of human diabetic UTI and can provide a powerful tool for dissecting this infection in the multifactorial setting of diabetes.
Rosen
David A
DA
Department of Molecular Microbiology, Washington University School of Medicine, St Louis, Missouri 63110, USA.
Hung
Chia-Suei
CS
Kline
Kimberly A
KA
Hultgren
Scott J
SJ
D000818:Animals; D003921:Diabetes Mellitus, Experimental; D004195:Disease Models, Animal; D013293:Enterococcus faecalis / Q000254:growth & development; D004926:Escherichia coli / Q000254:growth & development; D005260:Female; D016905:Gram-Negative Bacterial Infections / Q000382:microbiology* / Q000473:pathology; D016908:Gram-Positive Bacterial Infections / Q000382:microbiology* / Q000473:pathology; D007668:Kidney / Q000382:microbiology; D007684:Kidney Tubules / Q000382:microbiology / Q000473:pathology; D007711:Klebsiella pneumoniae / Q000254:growth & development; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D001743:Urinary Bladder / Q000382:microbiology; D014552:Urinary Tract Infections / Q000382:microbiology*