Adhesin regulatory genes within large, unstable DNA regions of pathogenic Escherichia coli: cross‐talk between different adhesin gene clusters

Joachim Morschhäuser, Viktoria Vetter, Levente Emödy, Jörg Hacker

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62 Citations (Scopus)

Abstract

The uropathogenic Escherichia coli strain 536 possesses two large, unstable DNA regions on its chromosome, which were termed pathogenicity islands (pais). Deletions of pais, which occur with relatively high frequency in vitro and in vivo, lead to avirulent mutants. The genetic determinants for production of haemolysin (Hly) and P‐related fimbriae (Prf) are located in one of these islands. Deletion of this pathogenicity isiand (paill) not only removes the hly‐ and prf‐specific genes, but also represses S fimbriae (Sfa), although the sfa genes of this virulence factor are not located on paill. We have identified two regulatory genes, prfB and prfl, of the prf gene cluster that are homologous to the sfa regulatory genes staB and SfaC, respectively. Mutations in sfaB and sfaC that inhibit transcription of the major fimbrial subunit gene sfaA were complemented by the homologous prf genes, suggesting communication between the two fimbrial gene clusters in the wild‐type strain. Chromosomal mutagenesis of the two prf regulators in strain 536 repressed transcription of sfaA, detected by Northern hybridization and a chromosomal sfaA‐lacZ fusion. In addition, haemagglutination assays measured a lower level of S fimbriae in these mutants. Expression of the cloned prf regulators in trans reversed the effect of the mutations; furthermore, constitutive expression of prfB or prfl could also overcome the repression of S fimbriae in a strain that had lost the pathogenicity islands. Virulence assays in mice established that the prf mutants were less virulent than the wild‐type strain. The results demonstrate that cross‐regulation of two unlinked virulence gene clusters together with the co‐ordinate loss of large DNA regions significantly influences the virulence of an extraintestinal E. coli wild‐type isolate.

Original languageEnglish
Pages (from-to)555-566
Number of pages12
JournalMolecular Microbiology
Volume11
Issue number3
DOIs
Publication statusPublished - Feb 1994

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology

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