Biphasic intracellular expression of Staphylococcus aureus virulence factors and evidence for Agr-mediated diffusion sensing

Sankale Shompole, Kim T. Henon, Linda E. Liou, Katarzyna Dziewanowska, Gregory A. Bohach, Kenneth W. Bayles

Research output: Contribution to journalArticle

59 Scopus citations

Abstract

Staphylococcus aureus invades a variety of mammalian cells and escapes from the endosome to multiply in the cytoplasm. We had previously hypothesized that the molecular events leading to escape of S. aureus from the endosome involved the Agr virulence factor regulatory system. In this report we demonstrate that temporal changes in intracellular activation of the Agr regulon correlates with expression of membrane active toxins. Also, the initial expression of Agr by even small numbers of staphylococci resulted in the permeabilization of the endosomal membrane and the eventual escape of bacteria into the cytoplasm by 3 h post invasion. After Agr downregulation, a second peak of expression coincided with increased permeability of the host cell membrane. In contrast to the parental strain, an Agr-mutant was unable to escape into the cytoplasm and was observed in intact endosomes as late as 5 h post invasion. These data provide evidence that staphylococcal virulence factor production during invasion of host cells is mediated by an Agr-dependent process that is most accurately described in the context of diffusion sensing.

Original languageEnglish (US)
Pages (from-to)919-927
Number of pages9
JournalMolecular Microbiology
Volume49
Issue number4
DOIs
StatePublished - Aug 2003

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology

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