The Asymptomatic BacteriuriaEscherichia coliStrain 83972 Outcompetes UropathogenicE. coliStrains in Human Urine

Abstract

Escherichia coli is the most common organism associated with asymptomatic bacteriuria (ABU). In contrast to uropathogenic E. coli (UPEC), which causes symptomatic urinary tract infections (UTI), very little is known about the mechanisms by which these strains colonize the human urinary tract. The prototype ABU E. coli strain 83972 was originally isolated from a girl who had carried it asymptomatically for 3 years. Deliberate colonization of UTI-susceptible individuals with E. coli 83972 has been used successfully as an alternative approach for the treatment of patients who are refractory to conventional therapy. Colonization with strain 83972 appears to prevent infection with UPEC strains in such patients despite the fact that this strain is unable to express the primary adhesins involved in UTI, viz. P and type 1 fimbriae. Here we investigated the growth characteristics of E. coli 83972 in human urine and show that it can outcompete a representative spectrum of UPEC strains for growth in urine. The unique ability of ABU E. coli 83972 to outcompete UPEC in urine was also demonstrated in a murine model of human UTI, confirming the selective advantage over UPEC in vivo.Comparison of global gene expression profiles of E. coli 83972 grown in lab medium and human urine revealed significant differences in expression levels in the two media; significant down-regulation of genes encoding virulence factors such as hemolysin, lipid A, and capsular polysaccharides was observed in cells grown in urine. Clearly, divergent abilities of ABU E. coli and UPEC to exploit human urine as a niche for persistence and survival suggest that these key differences may be exploited for preventative and/or therapeutic approaches.

Environmental phosphate differentially affects virulence phenotypes of uropathogenicEscherichia coliisolates causative of prostatitis

“…47 Interestingly, UPEC strains causative of asymptomatic bacteriuria, while lacking classical virulence factors such as fimbriae, express the full complement of iron acquisition systems, providing further evidence for the requirement of iron uptake during successful urinary tract colonization. 48 Fluoroquinolones have been the antimicrobial treatment of choice in febrile and acute UTIs. [49][50][51][52] Thus, susceptibility to nalidixic acid and ciprofloxacin was tested.…”

Innate Transcriptional Networks Activated in Bladder in Response to Uropathogenic Escherichia coli Drive Diverse Biological Pathways and Rapid Synthesis of IL-10 for Defense against Bacterial Urinary Tract Infection

“…The murine model of UTI utilizing female C57BL/6 mice (8-10 wk; The Jackson Laboratory [Bar Harbor, ME], Animal Resources Centre [Canning Vale, WA]) based on transurethral inoculation is described elsewhere (24)(25)(26)(27). IL-10-deficient B6.129P2-Il10 tm1Cgn/J mice (002251) were purchased with appropriate control mice (000664, C57BL/6J) from The Jackson Laboratory.…”

Preventing canine urinary tract infection (UTI) using an asymptomatic bacteriuria (ASB) Escherichia coli strain

“…There has been much interest in the characteristics of E. coli 83972 that allow it to persist in the urine for prolonged periods and in an attempt to better describe E. coli 83972, Roos et al (2006b) carried out a series of experiments including growth and competition experiments, and global gene expression profiles of E. coli 83972 grown in urine and laboratory media. E. coli 83972 was found to grow faster in urine than a variety of uropathogenic E. coli and to substantially outcompete each strain when urine was inoculated with equal amounts of each (E. coli 83972 comprised 71-97% of the population with overnight growth).…”

“…In order for prophylactic colonisation of dogs with E. coli 83972 to be successful, however, both long-term colonisation of the canine bladder and the ability to outcompete invading uropathogenic E. coli (UPEC) would be essential. Previously reported E. coli 83972 competition experiments performed in human urine with human-origin uropathogens demonstrated E. coli 83972 to be competitively superior, likely underpinning its success in prevention of recurrent UTI (Roos et al, 2006b), but it is unknown whether such success is replicable in competition experiments against canine uropathogens in pooled canine urine.…”

“…Further to this, possible explanations for any superior competition ability of E. coli 83972 in canine urine, such as enhanced iron-acquisition (Roos et al, 2006b;Watts et al, 2012), bear exploration. Escherichia coli 83972 siderophore (small, high-affinity iron chelating compounds secreted by bacteria) mutants have previously been shown to be outcompeted by the wild-type strain in an iron-limited medium, suggesting that iron acquisition may play an important role in the competitive performance of E. coli 83972 in human urine (Watts et al, 2012).…”