Involvement of Ca²+ signaling in intracellular invasion of non-phagocytic host cells by Orientia tsutsugamushi

Microb Pathog. 2011 Jun;50(6):326-30. doi: 10.1016/j.micpath.2011.02.007. Epub 2011 Mar 6.

Abstract

Calcium signaling has been implicated in various steps in bacterial pathogenesis. Here, we investigated the role of Ca(2+) signaling in intracellular invasion of non-phagocytic host cells infected with Orientia tsutsugamushi, the causative agent of scrub typhus. The bacteria induced a transient Ca(2+) increase in HeLa cells immediately after infection and the source of the mobilized Ca(2+) appears to be intracellular stores, not the extracellular milieu, as determined using extracellular (EGTA) or intracellular (BAPTA-AM) Ca(2+) chelators. O. tsutsugamushi rapidly induced activation of PLC-γ1, as indicated by tyrosine phosphorylation. PLC-γ1 activity increased within 1 min of infection and returned to the basal level by 5 min. Pretreatment of host cells with inhibitors of PLC-γ1 (U73122) or IP3R channel activity (2-APB) significantly blocked bacterial entry without affecting bacterial attachment. In addition, these chemical inhibitors were effective in suppressing not only the activation of ERK MAP kinase but also the expression of the chemokine MCP-1. Taken together, Ca(2+) signaling induced by O. tsutsugamushi may play a crucial role in bacterial pathogenesis including inflammatory reactions as well as intracellular invasion into non-phagocytic host cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Boron Compounds / pharmacology
  • Calcium / antagonists & inhibitors
  • Calcium / metabolism
  • Calcium Signaling / drug effects
  • Calcium Signaling / physiology*
  • Chelating Agents / pharmacology
  • Chemokines / biosynthesis
  • Chemokines / metabolism
  • Egtazic Acid / analogs & derivatives
  • Egtazic Acid / pharmacology
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • HeLa Cells
  • Host-Pathogen Interactions
  • Humans
  • Orientia tsutsugamushi / drug effects
  • Orientia tsutsugamushi / metabolism*
  • Orientia tsutsugamushi / pathogenicity*
  • Phagocytes / metabolism
  • Phospholipase C gamma / antagonists & inhibitors
  • Phospholipase C gamma / metabolism
  • Phosphorylation
  • Scrub Typhus / metabolism*
  • Scrub Typhus / microbiology
  • Tyrosine / metabolism

Substances

  • Boron Compounds
  • Chelating Agents
  • Chemokines
  • 1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester
  • Tyrosine
  • Egtazic Acid
  • 2-aminoethoxydiphenyl borate
  • Extracellular Signal-Regulated MAP Kinases
  • Phospholipase C gamma
  • Calcium