Characterization of Asymptomatic Bacteriuria Escherichia coli Isolates in Search of Alternative Strains for Efficient Bacterial Interference against Uropathogens

Abstract

Asymptomatic bacterial colonization of the urinary bladder (asymptomatic bacteriuria, ABU) can prevent bladder colonization by uropathogens and thus symptomatic urinary tract infection (UTI). Deliberate bladder colonization with Escherichia coli ABU isolate 83972 has been shown to outcompete uropathogens and prevent symptomatic UTI by bacterial interference. Many ABU isolates evolved from uropathogenic ancestors and, although attenuated, may still be able to express virulence-associated factors. Our aim was to screen for efficient and safe candidate strains that could be used as alternatives to E. coli 83972 for preventive and therapeutic bladder colonization. To identify ABU E. coli strains with minimal virulence potential but maximal interference efficiency, we compared nine ABU isolates from diabetic patients regarding their virulence- and fitness-associated phenotypes in vitro, their virulence in a murine model of sepsis and their genome content. We identified strains in competitive growth experiments, which successfully interfere with colonization of ABU isolate 83972 or uropathogenic E. coli strain 536. Six isolates were able to outcompete E. coli 83972 and two of them also outcompeted UPEC 536 during growth in urine. Superior competitiveness was not simply a result of better growth abilities in urine, but seems also to involve expression of antagonistic factors. Competitiveness in urine did not correlate with the prevalence of determinants coding for adhesins, iron uptake, toxins, and antagonistic factors. Three ABU strains (isolates 61, 106, and 123) with superior competitiveness relative to ABU model strain 83972 display low in vivo virulence in a murine sepsis model, and susceptibility to antibiotics. They belong to different phylogroups and differ in the presence of ExPEC virulence- and fitness-associated genes. Importantly, they all lack marked cytotoxic activity and exhibit a high LD50 value in the sepsis model. These strains represent promising candidates for a more detailed assessment of relevant fitness traits in urine and their suitability for therapeutic bladder colonization.

ClbR Is the Key Transcriptional Activator of Colibactin Gene Expression in Escherichia coli

“…The length requirement was set to a minimum of 60% sequence coverage for both serotyping and identification of resistance genes. For the determination of virulence factors (VFs), we used the E. coli VF collection (v0.1), which comprises 12 distinct VF groups containing 1,154 deduced protein sequences of virulence-associated genes ( 69 ).…”

Fimbriae reprogram host gene expression – Divergent effects of P and type 1 fimbriae

“…To address to what extent pap reconstitution in an ABU strain creates a disease-like response [7, 8, 37–39], we compared the repertoire of regulated genes in P V at the time of symptoms to the in vitro response of human kidney cells to the genetically closely related UPEC strain CFT073 (both phylogroup B2 and same sequence type) [13, 40]. A total of 115 genes were commonly regulated, including IRF7 and genes involved in interferon- and pattern recognition signaling ( S10 Fig ), suggesting that E .…”

Frequency of bacteriuria in dogs with chronic kidney disease: A retrospective study of 201 cases

“…The high frequency of E. coli in our study could be another explanation for the high prevalence of asymptomatic bacteriuria in our population. In addition, some studies in humans have shown that asymptomatic bacterial colonization of the bladder can prevent symptomatic UTI caused by the colonization of the urinary bladder by more virulent strains . Indeed, this prophylactic alternative to antimicrobial treatment also has been tested in dogs …”