CORRELATIONS BETWEEN MYCOPLASMA-PNEUMONIAE SENSITIVITY TO CYCLOSPORINE-A AND CYCLOPHILIN-MEDIATED REGULATION OF MYCOPLASMA CYTADHERENCE

Adhesins and adhesin-related accessory proteins of the bacterial patho gen, Mycoplasma pneumoniae, are proline-rich in composition and mediat e successful parasitism of host target cells. A specific class of pept idyl-proyl cis-trans isomerases (PPIs), called cyclophilins (Cyps), ac tivate proline-rich proteins, and this enzymatic activity is inhibited by the drug, cyclosporin A (CsA). This study builds upon the connecti on between the structural/functional properties of the proline-rich pr oteins of M. pneumoniae and the mode of action of CsA to demonstrate t hat CsA reduces cytadherence capabilities of mycoplasmas, affects colo ny morphology and can be mycoplasmacidal. As a consequence of CsA trea tment early passage mycoplasmas lacked the major adhesin, P1, explaini ng their cytadherence-negative phenotype. Three mycoplasma proteins wi th molecular masses of 160, 84 and 80 kDa were identified by CsA-affin ity chromatography. A PCR cloned partial cyp gene of M. pneumoniae, wh ich exhibited sequence homologies with prokaryotic and eukaryotic cycl ophilins, was present in multiple copies. These results implicate the role of PPIs as important regulators of cytadherence, virulence and gr owth cycle events in mycoplasmas. (C) 1996 Academic Press Limited