Yeaman M R, Ibrahim A S, Edwards J E, Bayer A S, Ghannoum M A
Department of Medicine, University of California-Los Angeles School of Medicine, Torrance, 90509.
Antimicrob Agents Chemother. 1993 Mar;37(3):546-53. doi: 10.1128/AAC.37.3.546.
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.
血小板杀菌蛋白（PMP）在凝血酶刺激下从血小板中释放出来。已知PMP在体外对金黄色葡萄球菌和草绿色链球菌具有杀菌活性。为了确定PMP对其他血管内病原体是否有活性，我们评估了其对念珠菌属菌株和新型隐球菌的潜在杀真菌活性。阴离子树脂吸附和凝胶电泳证实，PMP的杀真菌活性存在于一种小的（约8.5 kDa）阳离子蛋白中，这与之前关于PMP诱导细菌杀伤的研究一致（M.R. Yeaman、S.M. Puentes、D.C. Norman和A.S. Bayer，《感染与免疫》60:1202 - 1209，1992）。在体外180分钟的检测期间，这些真菌对PMP的敏感性差异很大。一般来说，白色念珠菌菌株（平均存活率，33.5% +/- 6.9% [n = 6]）以及光滑念珠菌分离株（平均存活率，50.8% +/- 2.9% [n = 2]）对PMP杀伤最为敏感，而季也蒙念珠菌和近平滑念珠菌对PMP诱导的杀伤相对耐药。与白色念珠菌相比，新型隐球菌对PMP的杀真菌活性相对耐药，在所研究的分离株中平均存活率为77.4% +/- 12.4%（n = 6）。针对白色念珠菌，PMP诱导的杀真菌活性具有时间依赖性（范围，0至180分钟）、PMP浓度依赖性（范围，10至150 U/ml），并且与真菌接种量呈负相关（范围，5×10³至1×10⁵ CFU/ml）。对暴露于PMP的白色念珠菌和新型隐球菌细胞进行扫描电子显微镜检查发现，其表面有广泛损伤和塌陷，这表明PMP杀真菌作用的位点可能直接或间接涉及真菌细胞包膜。
