Nonobstructive acute pyelonephritis in humans is most often caused by P-fimbriated Escherichia cofl. P-fimbriae are heteropolymeric fibers carrying a Gal(al-4)Gal-specific PapG adhesin at its distal end. The pyelonephritic strain DS17 expresses P-fimbriae from a single gene cluster. A mutant strain, DS17-8, which expresses P-fimbriae lacking the PapG adhesin, was constructed by allelic replacement introducing a 1-bp deletion early in the papG gene. In cynomolgus monkeys, DS17 and DS17-8 were equally able to cause bladder infection, whereas only the wild-type strain DS17 could cause pyelonephritis as monitored by bacteriological, functional, and histopathological criteria. Since DS17, but not DS17-8, adheres to renal tissue, these data underscore the critical role of microbial adherence to host tissues in infectious disease and strongly suggest that the PapG tip adhesin of P-fimbriae is essential in the pathogenesis of human kidney infection.
Purified PapDG is a tractable vaccine candidate that in our small study demonstrated the ability to elicit adequate serum antibody levels to prevent E. coli mediated pyelonephritis.
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