P-fimbriae trigger mucosal responses to Escherichia coli 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.
Wullt
B
B
Department of Microbiology, Lund University, Sölvegatan 23, S-223 62 Lund, Sweden.
Bergsten
G
G
Connell
H
H
Röllano
P
P
Gebratsedik
N
N
Hang
L
L
Svanborg
C
C
D015169:Colony Count, Microbial; D004926:Escherichia coli / Q000472:pathogenicity*; D004927:Escherichia coli Infections / Q000382:microbiology*; D005260:Female; D010861:Fimbriae, Bacterial / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D008297:Male; D009092:Mucous Membrane / Q000382:microbiology*; D014551:Urinary Tract / Q000276:immunology / Q000382:microbiology*; D014552:Urinary Tract Infections / Q000382:microbiology*; D014774:Virulence