Inhibition of macrophage autophagy induced by Salmonella enterica serovar typhi plasmid

Front Biosci (Landmark Ed). 2014 Jan 1;19:490-503. doi: 10.2741/4220.

Abstract

pR(ST98), a chimeric plasmid isolated from Salmonella enterica serovar typhi (S. typhi), is involved in bacterial multidrug-resistance and virulence, however, its exact contributions to bacterial pathogenesis are still not fully understood. To investigate whether pR(ST98) exhibits potential to mediate macrophage autophagy and apoptosis, murine macrophage-like cell line (J774A.1) was infected with wild type strain (S. typhi-WT), mutant strain (S. typhi-DeltapR(ST98)) and complement of S. typhi-DeltapR(ST98) (S. typhi-c-pR(ST98)). Results revealed that S. typhi harboring pR(ST98) decreased the number of autophagy vacuoles of macrophages as well as the expression of Beclin 1 and LC3-II at the early stage of infection; apoptosis rate of macrophages infected with S. typhi-DeltapR(ST98) was lower than that infected with S. typhi-WT or S. typhi-c-pR(ST98). The survival rate of intracellular bacteria carrying pR(ST98) was much higher than that of plasmid free strain. After intervention with autophagy agonist rapamycin, apoptosis rate of the cells infected with S. typhi containing pR(ST98) and intracellular bacterial growth decreased. Our study suggested that pR(ST98) could inhibit autophagy and induce cell apoptosis for the host bacterial survival and proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autophagy*
  • Base Sequence
  • Cell Line
  • DNA Primers
  • Macrophages / immunology*
  • Mice
  • Microscopy, Electron, Transmission
  • Plasmids*
  • Polymerase Chain Reaction
  • Salmonella enterica / physiology*
  • Salmonella enterica / ultrastructure

Substances

  • DNA Primers