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

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 island (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 sfaB 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 over-come 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.

Transcriptional analysis of the divergent cagAB genes encoded by the pathogenicity island of Helicobacter pylori

“…The potential coding of this DNA element has characteristics typical of the so-called pathogenicity islands, which have recently been described for other pathogenic bacteria, such as E. coli (Morschhä user et al, 1994;Ritter et al, 1995) and Salmonella typhimurium (Mills et al, 1995;Shea et al, 1996). Molecular genetic studies indicate that full virulence of these pathogens depends on the expression of genes encoded by their pathogenicity islands.…”

Self-perpetuating epigenetic pili switches in bacteria

“…Many uropathogenic E. coli contain multiple pili operons, many of which share the core control mechanisms of the pap operon including cross-complementing PapI and PapB homologues. Analysis of the pap-related fimbiae (prf ) operon of the uropathogenic E. coli strain 536 showed that deletion of the prfI and prfB genes, homologues of papI and papB, reduced the expression of S pili encoded by the unlinked sfa operon (32). Introduction of constitutively expressed PrfB or PrfI restored S pili expression, indicating that cross-activation of sfa was occurring.…”

Epigenetic Gene Regulation in the Bacterial World

“…Each of these pilus operons codes for a PapI and a PapB homologue, and cross-complementation between the PapB and PapI homologues between prf and sfa (182) and between pap and sfa and daa (267) was shown. The DaaF and SfaC proteins function similarly to PapI, positively regulating expression of daa and sfa, respectively, by facilitating binding of Lrp to promoter-distal binding sites overlapping GATC dist (267).…”