The role of lipopolysaccharide (LPS) and Shiga-like toxin (SLT) in the pathogenesis of hemolytic uremic syndrome (HUS) was studied in a mouse model. Mice inoculated intragastrically with Escherichia coli O157:H7 developed gastrointestinal, neurologic, and systemic symptoms, necrotic foci in the colon, glomerular and tubular histopathology, and fragmented erythrocytes. LPS-responder (C3H/HeN) mice developed a combination of neurologic and systemic symptoms, whereas LPS-nonresponder (C3H/HeJ) mice had a biphasic course of disease, first developing systemic symptoms and later severe neurologic symptoms. Mice inoculated with SLT-II-positive strains developed severe neurotoxic symptoms and a higher frequency of systemic symptoms and glomerular pathology compared with SLT-II-negative strains. Anti-SLT-II antibodies protected against these symptoms and pathology. These results demonstrate that this model could be used to study aspects of human HUS and that both LPS and SLT are important for disease development.

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.

This prospective study analyzed the intestinal carriage of P fimbriated Escherichia coli as a host susceptibility factor in urinary tract infection (UTI). P fimbriation was defined by the pap and G adhesin (papG1A2, prsGJ96) genotypes. Children with UTI carried pap+ E. coli in the fecal flora more often than healthy controls both at diagnosis (86% vs. 29%) and during infection-free intervals (approximately 40%; P < .01). P1 blood group-positive children carried pap+ E. coli in the fecal flora more often (88%) than those with P2 blood group (40%; P < .05). A pap+ E. coli strain caused UTI in 53 of 55 patients who carried both pap+ and pap- strains in their fecal flora. These results suggest that persons who develop UTI have an increased tendency to carry pap+ E. coli in the large intestine and that these pap+ E. coli cause UTI more often than pap E. coli strains in the fecal flora of the same host.

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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.