title: Thrombin-induced rabbit platelet microbicidal protein is fungicidal in vitro.
abstract: Platelet microbicidal protein (PMP) is released from platelets in response to thrombin stimulation. PMP is known to possess in vitro bactericidal activity against Staphylococcus aureus and viridans group streptococci. To determine whether PMP is active against other intravascular pathogens, we evaluated its potential fungicidal activity against strains of Candida species and Cryptococcus neoformans. Anionic resin adsorption and gel electrophoresis confirmed that the fungicidal activity of PMP resided in a small (approximately 8.5-kDa), cationic protein, identical to previous studies of PMP-induced bacterial killing (M.R. Yeaman, S.M. Puentes, D.C. Norman, and A.S. Bayer, Infect. Immun. 60:1202-1209, 1992). When assayed over a 180-min period in vitro, the susceptibilities of these fungi to PMP varied considerably. Generally, Candida albicans strains (mean survival, 33.5% +/- 6.9% [n = 6]) as well as isolates of Candida glabrata (mean survival, 50.8% +/- 2.9% [n = 2]) were the most susceptible to killing by PMP, while Candida guillermondii and Candida parapsilosis were relatively resistant to PMP-induced killing. Compared with C. albicans, C. neoformans was relatively resistant to the fungicidal activity of PMP, with a mean survival among the isolates studied of 77.4% +/- 12.4% (n = 6). Against C. albicans, PMP-induced fungicidal activity was time dependent (range, 0 to 180 min), PMP concentration dependent (range, 10 to 150 U/ml), and inversely related to the fungal inoculum (range, 5 x 10(3) to 1 x 10(5) CFU/ml). Scanning electron microscopy of PMP-exposed C. albicans and C. neoformans cells revealed extensive surface damage and collapse, suggesting that the site of PMP fungicidal action may directly or indirectly involve the fungal cell envelope.
authors: Department of Medicine, University of California-Los Angeles School of Medicine, Torrance, 90509.
authors: M R
authors: MR
authors: Yeaman
authors: A S
authors: AS
authors: Ibrahim
authors: J E
authors: JE
authors: Edwards
authors: A S
authors: AS
authors: Bayer
authors: M A
authors: MA
authors: Ghannoum
mesh_terms: D000666:Amphotericin B / Q000494:pharmacology; D000818:Animals; D000935:Antifungal Agents / Q000032:analysis / Q000494:pharmacology*; D001770:Blood Bactericidal Activity / Q000187:drug effects*; D001798:Blood Proteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000494:pharmacology*; D002175:Candida / Q000187:drug effects / Q000648:ultrastructure; D003455:Cryptococcus neoformans / Q000187:drug effects / Q000648:ultrastructure; D004352:Drug Resistance, Microbial; D008826:Microbial Sensitivity Tests; D011817:Rabbits; D013499:Surface Properties / Q000187:drug effects; D013917:Thrombin / Q000494:pharmacology*
chemical_list: D000935:Antifungal Agents; D001798:Blood Proteins; C077150:platelet microbicidal protein, Oryctolagus cuniculus; D000666:Amphotericin B; D013917:Thrombin