Chlamydia trachomatis Mip‐like protein has peptidylprolyl cis/trans isomerase activity that is inhibited by FK506 and rapamycin and is implicated in initiation of chlamydial infection

Abstract

The Mip-like protein of Chlamydia trachomatis has sequence similarity with both the Mip protein of Legionella pneumophila, a virulence factor necessary for optimal intracellular infection, and FK506-binding proteins (FKBPs) of both prokaryotic and eukaryotic origin. FKBPs contain a site for peptidyl-prolyl cis/trans isomerase activity, which is blocked upon binding of the drugs, FK506 or rapamycin. In this paper we report that the recombinant chlamydial Mip-like protein exhibits a peptidyl-prolyl cis/trans isomerase activity which is inhibited by either rapamycin or FK506. To assess the role of the Mip-like protein in chlamydial infection, rapamycin or FK506 (25 microM), were used in either treatment of chlamydial organisms prior to inoculation, or were present at different intervals through the infection. Pretreatment of organisms alone reduced infectivity for McCoy cells by 30%, with inhibition rising to 80% on more prolonged exposure from 0 to 8h and 8 to 16h post-inoculation and declining thereafter. When drug was present during the developmental cycle at intervals from 0 to 24h post-inoculation abnormal chlamydiae were induced in residual inclusions. The results suggest that inhibition of the isomerase of the Mip-like protein interferes with one or more early events in the infective process that determine productive intracellular infection.

The Chlamydia trachomatis Mip-like protein is a lipoprotein

“…The chlamydial Mip-like protein is poorly surface exposed, and specific antibodies are nonneutralizing in the absence of complement (13). The Mip-like protein has also previously been shown to have peptidylprolyl cis/trans isomerase (PPIase) activity that is inhibitable upon binding by the immunosuppressive drug FK506 or rapamycin (12). In experiments in which organisms were treated with FK506 or rapamycin prior to infection and during the early stages of infection, infectivity for McCoy cells was significantly reduced (12).…”

“…The Mip-like protein has also previously been shown to have peptidylprolyl cis/trans isomerase (PPIase) activity that is inhibitable upon binding by the immunosuppressive drug FK506 or rapamycin (12). In experiments in which organisms were treated with FK506 or rapamycin prior to infection and during the early stages of infection, infectivity for McCoy cells was significantly reduced (12). These results suggest that inhibition of the isomerase of the Mip-like protein interferes with one or more early events in the infective process that determine productive intracellular infection and that the Mip-like protein may be important for optimal initiation of chlamydial infections, as with Mip of L. pneumophila.…”

A novel peptidyl‐prolyl cisltrans isomerase from Escherichia coli

“…From the same organism a cyclophilin of 18 kDa has been isolated, sequenced and tested for catalytic function in prolyl cisltruns isomerization [17] [20], Neisseria meningitidis [21] and Chlamydia trachoma-tis [22]. In addition some ORFs were identified coding for proteins with some similarity to the core region of cyclophilins or FKBPs in Salmonella typhimurium [23], Synechococcus sp.…”

FKBPs in bacterial infections

“…Inhibiting its PPIase activity with FK506 results in irregularities during inclusion body formation inside the host cell together with reduced infectivity (Lundemose et al, 1993b). Surface-exposed Mip-like proteins were also found in the important human pathogens Neisseria gonorrhoeae and N. meningitidis where they mediate persistence in macrophages or improve bacterial survival in the blood, respectively (Echenique-Rivera et al, 2011;Leuzzi et al, 2005).…”