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The asymptomatic bacteriuria Escherichia coli strain 83972 outcompetes uropathogenic E. coli strains in human urine - PubMed

Comparative Study

The asymptomatic bacteriuria Escherichia coli strain 83972 outcompetes uropathogenic E. coli strains in human urine

Viktoria Roos et al. Infect Immun. 2006 Jan.

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.

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Figures

FIG. 1.
FIG. 1.

(A) Growth of ABU E. coli 83972 and UPEC strains 536, CFT073, NU14, and 1177 in human urine. The curves are shown as means of triplicates, and error bars indicate standard deviations (σn1). (B) The doubling time during exponential phase for each strain was calculated and is shown as the mean of triplicates. Bars indicate standard deviations. (C) Competition experiment between 83972 and NU14 mixed 1:1 at the starting point in human urine. Values are means of duplicates, and error bars indicate standard deviations.

FIG. 2.
FIG. 2.

Results from growth competition experiments (1:1) between E. coli 83972 and UPEC strains after 17 h of growth in human urine. Each value is an average of four individual shake flasks obtained from two separate experiments in different batches of urine. In all four competition experiments, strain 83972 was present in significantly higher numbers than the UPEC isolate (paired two-tailed t test, P < 0.001).

FIG. 3.
FIG. 3.

Expression levels of iron acquisition systems (A) and adhesins (B) in E. coli 83972 grown in urine. The numbers indicate fold changes of expression levels for genes significantly changed in urine compared with MOPS. Asterisks indicate CFT073 transcripts in cases where there are two genes with the same name.

FIG. 4.
FIG. 4.

Transport and degradation pathways of the sugar acids galacturonate, glucuronide, and galactonate. The numbers indicate significant fold changes of expression levels for genes in E. coli 83972 grown in urine compared with the same cells grown in MOPS.

FIG. 5.
FIG. 5.

Results from mice (n = 7) challenged for 24 h with the UPEC isolate NU14 or E. coli 83972 and NU14 (1:1). (A) Mean total number of CFU per ml of urine ± the standard error of the mean; (B) percentages of NU14 and ABU 83972 calculated from differential colony counts. Total colony counts were not influenced by the presence of 83972. E. coli 83972 was present in significantly higher numbers in urine from mice compared with NU14 (98.7% versus 1.3%; paired two-tailed t test, P < 0.001).

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