title: A Burkholderia pseudomallei macrophage infectivity potentiator-like protein has rapamycin-inhibitable peptidylprolyl isomerase activity and pleiotropic effects on virulence.
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.
authors.affiliation: Defence Science and Technology Laboratory, Porton Down SP4 0JQ, UK. ihnorville@dstl.gov.uk
authors.forename: Isobel H
authors.initials: IH
authors.lastname: Norville
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Harmer
authors.forename: Sarah V
authors.initials: SV
authors.lastname: Harding
authors.forename: Gunter
authors.initials: G
authors.lastname: Fischer
authors.forename: Karen E
authors.initials: KE
authors.lastname: Keith
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Brown
authors.forename: Mitali
authors.initials: M
authors.lastname: Sarkar-Tyson
authors.forename: Richard W
authors.initials: RW
authors.lastname: Titball
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016957:Burkholderia pseudomallei / Q000378:metabolism* / Q000472:pathogenicity*; D015964:Gene Expression Regulation, Bacterial; D051379:Mice; D008807:Mice, Inbred BALB C; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019696:Peptidylprolyl Isomerase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011487:Protein Conformation; D011994:Recombinant Proteins; D020123:Sirolimus / Q000494:pharmacology*; D022021:Tacrolimus Binding Proteins / Q000235:genetics / Q000378:metabolism; D014774:Virulence
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D011994:Recombinant Proteins; D022021:Tacrolimus Binding Proteins; D019696:Peptidylprolyl Isomerase; D020123:Sirolimus