Abstract
This study aimed to provide evidence of persistent uropathogenic Escherichia coli (UPEC) in female patients with recurrent urinary tract infection (UTI) after antibiotic therapy. We collected biopsies of the bladder, and clean-catch urine samples from 32 women who had episodes of recurrent UTI and were given antibiotic therapy. Urine samples and biopsies were analyzed by conventional bacteriological techniques. Phylogenetic group and 16 virulence factors (VFs) of UPEC were determined using polymerase chain reaction (PCR). The infection capability of UPEC was confirmed in a mouse model. Immunofluorescence and electron microscopy were used to detect intracellular bacterial communities (IBCs) in the mouse model. The results showed that all urine specimens were detected sterile. E. coli was found in 6 of 32 biopsies (18.75%), and was identified to be UPEC by PCR. Different VFs associated with the formation of IBCs were identified in all six UPEC isolates. Each UPEC isolate was capable of forming IBCs within the bladder epithelial cells of mice. In conclusion, UPEC with distinctive pathological traits and the capability of IBC formation was first found in the bladders of women after antibiotic therapy, suggesting that the IBC pathogenic pathway may occur in humans and it plays an important role in UTI recurrence.
Similar content being viewed by others
References
Liu X, Chen Z, Ye Z. Etiological study on cystitis glandularis caused by bacterial infection. J Huazhong Univ Sci Technol [Med Sci], 2007,27(6):678–680
Chen Z, Lan R, Ye Z, et al. Analysis on pathogenesis of 50 cases of bladder proliferative lesions. J Huazhong Univ Sci Technol [Med Sci], 2003,23(3):294–296
Foxman B. Recurring urinary tract infection: Incidence and risk factors. Am J Public Health, 1990,80(3):331–333
Scholes D, Hooton TM, Roberts PL, et al. Risk factors for recurrent urinary tract infection in young women. J Infect Dis, 2000,182(4):1177–1182
Ronald A, Nicolle L, Stamm E, et al. Urinary tract infection in adults: Research priorities and strategies. Int J Antimicrob Agents, 2001,17(4):343–348
Ronald A. The etiology of urinary tract infection: Traditional and emerging pathogens. Dis Mon, 2003,49(2):71–82
Anderson GG, Palermo JJ, Schilling JD, et al. Intracellular bacterial biofilm-like pods in urinary tract infections. Science, 2003,301(5629):105–107
Anderson GG, Dodson KW, Hooton TM, et al. Intracellular bacterial communities of uropathogenic escherichia coli in urinary tract pathogenesis. Trends Microbiol, 2004,12(9):424–430
Justice SS, Hung C, Theriot JA, et al. Differentiation and developmental pathways of uropathogenic escherichia coli in urinary tract pathogenesis. Proc Natl Acad Sci USA, 2004,101(5):1333–1338
Garofalo CK, Hooton TM, Martin SM, et al. Escherichia coli from urine of female patients with urinary tract infections is competent for intracellular bacterial community formation. Infect Immun, 2007,75(1):52–60
Mysorekar IU, Hultgren SJ. Mechanisms of uropathogenic escherichia coli persistence and eradication from the urinary tract. Proc Natl Acad Sci USA, 2006,103(38):14170–14175
Mulvey MA, Schilling JD, Hultgren SJ. Establishment of a persistent escherichia coli reservoir during the acute phase of a bladder infection. Infect Immun, 2001,69(7):4572–4579
Schilling JD, Lorenz RG, Hultgren SJ. Effect of trimethoprim-sulfamethoxazole on recurrent bacteriuria and bacterial persistence in mice infected with uropathogenic escherichia coli. Infect Immun, 2002,70(12):7042–7049
Blango MG, Mulvey MA. Persistence of uropathogenic escherichia coli in the face of multiple antibiotics. Antimicrob Agents Chemother, 2010,54(5):1855–1863
Johnson JR. Virulence factors in escherichia coli urinary tract infection. Clin Microbiol Rev, 1991,4(1):80–128
Johnson JR, Stell AL. Extended virulence genotypes of escherichia coli strains from patients with urosepsis in relation to phylogeny and host compromise. J Infect Dis, 2000,181(1):261–272
Clermont O, Bonacorsi S, Bingen E. Rapid and simple determination of the escherichia coli phylogenetic group. Appl Environ Microbiol, 2000,66(10):4555–4558
Johnson JR, Kuskowski MA, Owens K, et al. Phylogenetic origin and virulence genotype in relation to resistance to fluoroquinolones and/or extendedspectrum cephalosporins and cephamycins among escherichia coli isolates from animals and humans. J Infect Dis, 2003,188(5):759–768
Bower JM, Eto DS, Mulvey MA. Covert operations of uropathogenic escherichia coli within the urinary tract. Traffic, 2005,6(1):18–31
Rosen DA, Hooton TM, Stamm WE, et al. Detection of intracellular bacterial communities in human urinary tract infection. PLoS Med, 2007,4(12):e329
Robino L, Scavone P, Araujo L, et al. Detection of intracellular bacterial communities in a child with escherichia coli recurrent urinary tract infections. Pathog Dis, 2013,68(3):78–81
Robino L, Scavone P, Araujo L, et al. Intracellular bacteria in the pathogenesis of escherichia coli urinary tract infection in children. Clin Infect Dis, 2014,59(11): e158–164
Elliott TS, Reed L, Slack RC, et al. Bacteriology and ultrastructure of the bladder in patients with urinary tract infections. J Infect, 1985,11(3):191–199
Stamm WE, Counts GW, Running KR, et al. Diagnosis of coliform infection in acutely dysuric women. N Engl J Med, 1982,307(8):463–468
He XL, Wang Q, Peng L, et al. Role of uropathogenic escherichia coli outer membrane protein t in pathogenesis of urinary tract infection. Pathog Dis, 2015,73(3):ftv006
Hung C-S, Dodson KW, Hultgren SJ. A murine model of urinary tract infection. Nat Protoc, 2009,4(8):1230–1243
Martinez JJ, Mulvey MA, Schilling JD, et al. Type 1 pilus-mediated bacterial invasion of bladder epithelial cells. EMBO J, 2000,19(12):2803–2812
Dhakal BK, Kulesus RR, Mulvey MA. Mechanisms and consequences of bladder cell invasion by uropathogenic escherichia coli. Eur J Clin Invest, 2008,38(s2):2–11
Mulvey MA. Adhesion and entry of uropathogenic escherichia coli. Cell Microbiol, 2002,4(5):257–271
Mulvey MA, Lopez-Boado YS, Wilson CL, et al. Induction and evasion of host defenses by type 1-piliated uropathogenic escherichia coli. Science, 1998,282(5393):1494–1497
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Liu, Sc., Han, Xm., Shi, M. et al. Persistence of uropathogenic Escherichia Coli in the bladders of female patients with sterile urine after antibiotic therapies. J. Huazhong Univ. Sci. Technol. [Med. Sci.] 36, 710–715 (2016). https://doi.org/10.1007/s11596-016-1649-9
Received:
Revised:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11596-016-1649-9