(p)ppGpp regulates type 1 fimbriation of Escherichia coli by modulating the expression of the site-specific recombinase FimB

Mol Microbiol. 2006 Jun;60(6):1520-33. doi: 10.1111/j.1365-2958.2006.05191.x.

Abstract

In this report we have examined the role of the regulatory alarmone (p)ppGpp on expression of virulence determinants of uropathogenic Escherichia coli strains. The ability to form biofilms is shown to be markedly diminished in (p)ppGpp-deficient strains. We present evidence (i) that (p)ppGpp tightly regulates expression of the type 1 fimbriae in both commensal and pathogenic E. coli isolates by increasing the subpopulation of cells that express the type 1 fimbriae; and (ii) that the effect of (p)ppGpp on the number of fimbrial expressing cells can ultimately be traced to its role in transcription of the fimB recombinase gene, whose product mediates inversion of the fim promoter to the productive (ON) orientation. Primer extension analysis suggests that the effect of (p)ppGpp on transcription of fimB occurs by altering the activity of only one of the two fimB promoters. Furthermore, spontaneous mutants with properties characteristic of ppGpp(0) suppressors restore fimB transcription and consequent downstream effects in the absence of (p)ppGpp. Consistently, the rpoB3770 allele also fully restores transcription of fimB in a ppGpp(0) strain and artificially elevated levels of FimB bypass the need for (p)ppGpp for type 1 fimbriation. Our findings suggest that the (p)ppGpp-stimulated expression of type 1 fimbriae may be relevant during the interaction of pathogenic E. coli with the host.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Agglutination
  • Bacterial Proteins / metabolism
  • Biofilms / growth & development
  • DNA Nucleotidyltransferases / genetics
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Escherichia coli / drug effects
  • Escherichia coli / genetics
  • Escherichia coli / pathogenicity*
  • Escherichia coli Proteins / genetics*
  • Escherichia coli Proteins / metabolism
  • Fimbriae Proteins / genetics
  • Fimbriae, Bacterial / genetics
  • Gene Expression Regulation, Bacterial*
  • Guanosine Pentaphosphate / genetics
  • Guanosine Pentaphosphate / pharmacology
  • Guanosine Pentaphosphate / physiology*
  • Guanosine Tetraphosphate / genetics
  • Guanosine Tetraphosphate / pharmacology
  • Guanosine Tetraphosphate / physiology*
  • Integrases / genetics*
  • Mutation
  • Promoter Regions, Genetic / drug effects
  • Sigma Factor / metabolism
  • Suppression, Genetic
  • Transcription, Genetic / drug effects
  • Urologic Diseases / microbiology
  • Yeasts / cytology

Substances

  • Bacterial Proteins
  • DNA-Binding Proteins
  • Escherichia coli Proteins
  • H-NS protein, bacteria
  • NanR protein, E coli
  • Sigma Factor
  • fimB protein, E coli
  • fimbrillin
  • sigma factor KatF protein, Bacteria
  • Fimbriae Proteins
  • Guanosine Tetraphosphate
  • Guanosine Pentaphosphate
  • DNA Nucleotidyltransferases
  • Integrases
  • Site-specific recombinase