Chlamydia trachomatis Mip-like protein has peptidyl-prolyl cis/trans isomerase activity that is inhibited by FK506 and rapamycin and is implicated in initiation of chlamydial infection.
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.
Lundemose
A G
AG
Microbial Molecular Genetics, University of Birmingham, UK.
Kay
J E
JE
Pearce
J H
JH
D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002692:Chlamydia trachomatis / Q000187:drug effects / Q000201:enzymology* / Q000472:pathogenicity; D051379:Mice; D008969:Molecular Sequence Data; D011090:Polyenes / Q000494:pharmacology*; D011993:Recombinant Fusion Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D020123:Sirolimus; D016559:Tacrolimus / Q000494:pharmacology*; D022021:Tacrolimus Binding Proteins; D014774:Virulence / Q000235:genetics
D001426:Bacterial Proteins; D002352:Carrier Proteins; D011090:Polyenes; D011993:Recombinant Fusion Proteins; C077482:Mip-like protein, Chlamydia trachomatis; D022021:Tacrolimus Binding Proteins; D020123:Sirolimus; D016559:Tacrolimus