sirolimus and Gonorrhea

Macrophage infectivity potentiators (MIPs) are a family of surface-exposed virulence factors of intracellular microorganisms such as Legionella, Chlamydia and Trypanosoma. These proteins display peptidyl-prolyl cis/trans isomerase (PPIase) activity that is inhibited by immunosuppressants FK506 and rapamycin. Here we describe the identification and characterization in Neisseria gonorrhoeae of Ng-MIP, a surface-exposed lipoprotein with high homology to MIPs. The protein is an homodimer with rapamycin-inhibited PPIase activity confirming that it is a functional member of the MIP family. A knock-out strain, generated by deletion of the mip gene in N. gonorrhoeae F62 strain, was evaluated for its role in infection of mouse and human macrophages. We show that Ng-MIP promotes the intracellular survival of N. gonorrhoeae in macrophages, highlighting a possible role of this protein in promoting the persistence of gonococcal infection.

Topics: Amino Acid Sequence; Animals; Anti-Bacterial Agents; Bacterial Proteins; Cells, Cultured; Dimerization; Gene Deletion; Gonorrhea; Humans; Immunophilins; Lipoproteins; Macrophages; Membrane Proteins; Mice; Molecular Sequence Data; Neisseria gonorrhoeae; Peptidylprolyl Isomerase; Protein Binding; Protein Structure, Quaternary; Sequence Alignment; Sirolimus