SummaryThis study examined the role of P fimbriae in the establishment of bacteriuria. Patients (n 17) were subjected to intravesical inoculation with an asymptomatic bacteriuria strain, Escherichia coli 83972, or its P-fimbriated (pap 1 /prs 1 ) transformants. As shown by groupwise analysis, the pap 1 /prs 1 transformants established bacteriuria more rapidly than E. coli 83972 (P 0.021) and required a lower number of inoculations to reach 10 5 cfu ml 21 (P 0.018). Intraindividual analysis showed that the pap 1 /prs 1 transformants established bacteriuria more rapidly than E. coli 83972 in the patients who subsequently became carriers of both strains. Finally, bacterial establishment was shown to vary with the in vivo expression of P fimbriae. Bacterial counts were higher when P-fimbrial expression was detected than when the pap 1 /prs 1 strain showed a negative phenotype. The results suggested that P fimbriae enhance the establishment of bacteriuria and fulfil the molecular Koch postulates as a colonization factor in the human urinary tract.
Uropathogenic Escherichia coli elicit a host response that determines the severity of urinary tract infection (UTI). Specific adherence mechanisms allow the bacteria to initiate this process by targeting epithelial cells in the urinary tract mucosa. Epidemiological studies show a strong association of P-fimbriae with disease severity, suggesting that adherence mediated by these organelles has a direct effect on mucosal inflammation in vivo. The present study examined the ability of P-fimbriae to induce inflammation in the human urinary tract. Patients were subjected to intravesical inoculation with a non-fimbriated E. coli strain or transformants of this strain expressing P-fimbriae. The inflammatory response was analysed as a function of P-fimbrial expression. The P-fimbriated transformants invariably caused higher interleukin (IL)-8, IL-6 and neutrophil responses in the urinary tract than the ABU strain. Furthermore, loss of P-fimbrial expression in vivo was accompanied by a return to background levels of neutrophils, IL-6 and IL-8 in individual patients. The results demonstrate that the pap sequences confer on a non-fimbriated, avirulent strain the ability to induce a host response in the human urinary tract. P-fimbriae thus fulfil the 'molecular Koch-Henle postulates' linking a single virulence factor to host response induction.
E. coli 83972 bacteriuria could only be established in a subset of patients with defective bladder voiding, suggesting that urodynamic defects permit a nonvirulent strain to establish in the urinary tract, but that additional host factors determine if bacteriuria will persist.
E. coli 83972 bacteriuria could only be established in a subset of patients with defective bladder voiding, suggesting that urodynamic defects permit a nonvirulent strain to establish in the urinary tract, but that additional host factors determine if bacteriuria will persist.
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