Role of Host Type IA Phosphoinositide 3-Kinase Pathway Components in Invasin-Mediated Internalization of Yersinia enterocolitica

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Abstract
Many bacterial pathogens subvert mammalian type IA phosphoinositide 3-kinase (PI3K) in order to induce their internalization into host cells. How PI3K promotes internalization is not well understood. Also unclear is whether type PI3K affects different pathogens through similar or distinct mechanisms. Here we performed an RNA interference (RNAi)-based screen to identify components of the type IA PI3K pathway involved in invasin-mediated entry of Yersinia enterocolitica, an enteropathogen that causes enteritis and lymphadenitis. The 69 genes targeted encode known upstream regulators or downstream effectors of PI3K. A similar RNAi screen was previously performed with the food-borne bacterium Listeria monocytogenes. The results of the screen with Y. enterocolitica indicate that at least nine members of the PI3K pathway are needed for invasin-mediated entry. Several of these proteins, including Centaurin-α1, Dock180, FAK, Grp1, LL5α, LL5β, and PLD2 were recruited to sites of entry. In addition, Centaurin-α1, FAK, PLD2, and mTor were required for remodeling of the actin cytoskeleton during entry. Six of the human proteins affecting invasin-dependent internalization also promote InlB-mediated entry of L. monocytogenes. Our results identify several host proteins that mediate invasin-induced effects on the actin cytoskeleton and indicate that subset of PI3K pathway components promote internalization of both Y. enterocolitica and L. monocytogenes.
Funding Information
  • Lottery Health Research of New Zealand
  • Marsden Fund of the Royal Society of New Zealand (13-UOO-085)
  • University of Otago Research Committee

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