Varga V., Duchéne M., Tachezy J., Hrdý I., Kulda J., Thalhammer T. (2002). Cyclophylins of Trichomonas vaginalis. J. Eukaryot. Microbiol. 49: 9A-10A (Abstract 39) ISSN 1066-5234, IF 1,739
ABSTRACT. Cyclosporin A (CsA), initially developed as an immunosuppressive drug, possesses activity against various protozoan parasites in a species and/or stage specific manner. CsA binds to the high affinity intracellular receptors, cyclophilins (Cyps). The cyclophilins display the peptidyl-prolyl cis/trans isomerase activity and accelerate the rate-limiting step in the folding of target proteins. If CsA binds to Cyp, the CsA/Cyp complex inhibits calcineurin-mediated dephosphorylation of transcription factors, which in their phosphorylated form are unable to translocate in the nucleus. The present study was undertaken to characterize Cyps in Trichomonas vaginalis and to test the susceptibility of the parasite to CsA and related compounds. Using a CsA-affinity column an 18kDa protein was isolated from a cytosolic fraction of T. vaginalis. The protein was unglycosylated and peptide sequencing showed its high homology to Cyps of other parasites. The protein possessed peptidyl-prolyl cis/trans isomerase activity, inhibitable by CsA (IC50 ~ 10nM), indicating that this protein belongs to cyclophilins. Furthermore, the isoelectric focusing revealed two isoforms with an isoelectric point around 8.6, as observed for other cytosolic Cyps. Exposure of T. vaginalis to CsA for 24 and 48 hrs showed that CsA is toxic to the parasite at the minimal lethal concentration (MLC) of 60 µM. Interestingly, another CsA-derivative, the SDZ PSC833, which does not bind to the human cytosolic Cyp, was more effective than CsA (MLC about 7 µM). It indicates, that Cyp binding and inhibition of peptidyl-prolyl cis/trans isomerase activity might not be the only mechanism of the CsA action against T. vaginalis. Further studies are required to elucidate the physiological function of this novel T. vaginalis cyclophilin and to evaluate its potencial as a target for therapy.