A Burkholderia pseudomallei macrophage infectivity potentiator-like protein has rapamycin-inhibitable peptidylprolyl isomerase activity and pleiotropic effects on virulence

Infect Immun. 2011 Nov;79(11):4299-307. doi: 10.1128/IAI.00134-11. Epub 2011 Aug 22.

Abstract

Macrophage infectivity potentiators (Mips) are a group of virulence factors encoded by pathogenic bacteria such as Legionella, Chlamydia, and Neisseria species. Mips are part of the FK506-binding protein (FKBP) family, whose members typically exhibit peptidylprolyl cis-trans isomerase (PPIase) activity which is inhibitable by the immunosuppressants FK506 and rapamycin. Here we describe the identification and characterization of BPSS1823, a Mip-like protein in the intracellular pathogen Burkholderia pseudomallei. Recombinant BPSS1823 protein has rapamycin-inhibitable PPIase activity, indicating that it is a functional FKBP. A mutant strain generated by deletion of BPSS1823 in B. pseudomallei exhibited a reduced ability to survive within cells and significant attenuation in vivo, suggesting that BPSS1823 is important for B. pseudomallei virulence. In addition, pleiotropic effects were observed with a reduction in virulence mechanisms, including resistance to host killing mechanisms, swarming motility, and protease production.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Anti-Bacterial Agents / pharmacology*
  • Bacterial Proteins / antagonists & inhibitors
  • Bacterial Proteins / metabolism*
  • Burkholderia pseudomallei / metabolism*
  • Burkholderia pseudomallei / pathogenicity*
  • Gene Expression Regulation, Bacterial
  • Mice
  • Mice, Inbred BALB C
  • Models, Molecular
  • Molecular Sequence Data
  • Peptidylprolyl Isomerase / antagonists & inhibitors
  • Peptidylprolyl Isomerase / metabolism*
  • Protein Conformation
  • Recombinant Proteins
  • Sirolimus / pharmacology*
  • Tacrolimus Binding Proteins / genetics
  • Tacrolimus Binding Proteins / metabolism
  • Virulence

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Recombinant Proteins
  • Tacrolimus Binding Proteins
  • Peptidylprolyl Isomerase
  • Sirolimus