Src kinase has a central role in vitro cellular internalization of Staphylococcus aureus

Tent Fowler, Staffan Johansson, Kishore K. Wary, Magnus Höök

Research output: Contribution to journalArticle

44 Scopus citations

Abstract

Traditionally recognized as an extracellular pathogen, the Gram-positive bacterium Staphylococcus aureus can also be internalized by a variety of cell types in vitro. Internalization is known to involve binding of the host extracellular protein fibronectin to the bacterium, recognition of the fibronectin-coated bacterium by the fibronectin-binding integrin a5β1 on the host cell surface, and integrin-mediated internalization. Here we examine elements of mammalian cell signalling pathways involved In S. aureus internalization. The mouse fibroblast cell line GD25, in which the gene encoding the β1 integrin subunit is inactivated, has been complemented with a β1 integrin cDNA encoding a tyrosine (Y) to phenylalanine (F) mutation in each of the two β1 integrin intracellular NPXY motifs. This cell line, GD25β1 A Y783/795F, is defective in migration on fibronectin coated surfaces and intracellular signalling activities involving the tyrosine kinase Src. GD25β1 A Y783/795F cells have a decreased ability to internalize S. aureus compared to GD25β1 A cells expressing wild-type β1 integrins. Furthermore, using mouse embryo fibroblasts in which different members of the Src family kinases are genetically inactivated, we demonstrate that optimal internalization is dependent on expression of Src kinase. Interferon, which has been implicated in repression of the effects of the viral homologue of Src inhibits internalization of S. aureus indicating that internalization may be blocked by inhibitors of Src kinase function. We then demonstrate that Src family kinase specific inhibitors effectively block S. aureus internalization into HeLa cells leading to the conclusion that a function unique to Src is required for optimal internalization of S. aureus in vitro.

Original languageEnglish (US)
Pages (from-to)417-426
Number of pages10
JournalCellular Microbiology
Volume5
Issue number6
DOIs
StatePublished - Jun 1 2003

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Virology

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