P-fimbriae trigger mucosal responses to Escherichia coli in the human urinary tract

Abstract

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.

Renal Collecting Duct Epithelial Cells React to Pyelonephritis-Associated Escherichia coli by Activating Distinct TLR4-Dependent and -Independent Inflammatory Pathways

“…The mechanisms of interaction between UPECs and bladder epithelial cells have been extensively investigated (14,16,17). UPECs can also interact with renal tubule cells.…”

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

“…UPEC induces host cell apoptosis in cystitis patients (19)(20)(21) and macrophage inflammatory peptide 2 that is induced in response to neutrophils attracted to the bladder to counteract colonization by the bacterium (6). Specific UPEC adhesins, including type 1 and P fimbriae, trigger some of these processes (22,23). Host responses that arbitrate these very early steps in the pathogenesis of UPEC UTI are largely unknown, and the overall contributions of innate immune elements beyond previously identified mechanisms of attachment are not well defined.…”

Molecular Characterization of the Escherichia coli Asymptomatic Bacteriuria Strain 83972: the Taming of a Pathogen

“…The strain is a clinical isolate capable of long-term bladder colonization (1). It was isolated from a patient with ABU who had carried it for 3 years, and it has been used in colonization studies as a prophylactic agent to prevent UTI in humans (2,8,30,34,35).…”