Stevens David A, White Theodore C, Perlin David S, Selitrennikoff Claude P
Department of Medicine, Santa Clara Valley Medical Center, San Jose, CA 95128-2699, USA.
Diagn Microbiol Infect Dis. 2005 Mar;51(3):173-8. doi: 10.1016/j.diagmicrobio.2004.10.006.
Turbid growth of some Candida albicans isolates occurs, paradoxically, in some high concentrations of caspofungin, above the minimum inhibitory concentration. We show that the resistant phenotype is first detectable after 24 h of drug exposure. Although other studies have suggested an association between some azole resistance mechanisms and caspofungin resistance, our studies with isolates susceptible and resistant to azoles (the latter including groups with defined resistance mechanisms and derived mutants) suggest a weak association at most with a paradoxical effect. The paradoxical growth is not related to mutations in resistance-associated regions of the (1,3)-beta-glucan synthase complex and is not related to an up-regulation of (1,3)-beta-glucan synthase activity in the presence of drug. Subculture of a minority of tubes above the minimum fungicidal concentration yielded a few viable cells, suggesting random distribution, in some strains, of a few cells with propensity to grow in the presence of drug. We postulate high drug concentrations derepress or activate an as-yet undefined resistance mechanism(s).
矛盾的是，一些白色念珠菌分离株在高于最低抑菌浓度的某些高浓度卡泊芬净中会出现浑浊生长。我们发现，耐药表型在药物暴露24小时后首次可检测到。尽管其他研究表明某些唑类耐药机制与卡泊芬净耐药之间存在关联，但我们对唑类敏感和耐药分离株（后者包括具有明确耐药机制的群体和衍生突变体）的研究表明，两者之间至多存在微弱关联，且存在矛盾效应。矛盾生长与（1,3）-β-葡聚糖合酶复合物耐药相关区域的突变无关，也与药物存在时（1,3）-β-葡聚糖合酶活性上调无关。在少数高于最低杀菌浓度的试管中传代培养产生了一些活细胞，这表明在某些菌株中，少数有在药物存在下生长倾向的细胞呈随机分布。我们推测高药物浓度会解除抑制或激活一种尚未明确的耐药机制。
