Correlations between Mycoplasma pneumoniae sensitivity to cyclosporin A and cyclophilin-mediated regulation of mycoplasma cytadherence.
Adhesins and adhesin-related accessory proteins of the bacterial pathogen, Mycoplasma pneumoniae, are proline-rich in composition and mediate successful parasitism of host target cells. A specific class of peptidyl-proyl cis-trans isomerases (PPIs), called cyclophilins (Cyps), activate proline-rich proteins, and this enzymatic activity is inhibited by the drug, cyclosporin A (CsA). This study builds upon the connection between the structural/functional properties of the proline-rich proteins of M. pneumoniae and the mode of action of CsA to demonstrate that CsA reduces cytadherence capabilities of mycoplasmas, affects colony morphology and can be mycoplasmacidal. As a consequence of CsA treatment early passage mycoplasmas lacked the major adhesin, P1, explaining their cytadherence-negative phenotype. Three mycoplasma proteins with molecular masses of 160, 84 and 80 kDa were identified by CsA-affinity chromatography. A PCR cloned partial cyp gene of M. pneumoniae, which exhibited sequence homologies with prokaryotic and eukaryotic cyclophilins, was present in multiple copies. These results implicate the role of PPIs as important regulators of cytadherence, virulence and growth cycle events in mycoplasmas.
Reddy
S P
SP
Department of Microbiology, University of Texas Health Science Center at San Antonio 78284-7758, USA.
Rasmussen
W G
WG
Baseman
J B
JB
D000591:Amino Acid Isomerases / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D001422:Bacterial Adhesion; D001483:Base Sequence; D002352:Carrier Proteins / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D003001:Cloning, Molecular; D003524:Cyclosporins / Q000378:metabolism*; D004352:Drug Resistance, Microbial / Q000235:genetics; D006382:Hemadsorption; D015151:Immunoblotting; D008969:Molecular Sequence Data; D009177:Mycoplasma pneumoniae / Q000737:chemistry / Q000254:growth & development / Q000502:physiology; D019696:Peptidylprolyl Isomerase; D016133:Polymerase Chain Reaction; D014774:Virulence
D002352:Carrier Proteins; D003524:Cyclosporins; D000591:Amino Acid Isomerases; D019696:Peptidylprolyl Isomerase