形态区对抗真菌药物敏感性测试和毒力研究的影响。
Impact of Morphological Sectors on Antifungal Susceptibility Testing and Virulence Studies.
机构信息
Division of Hygiene and Medical Microbiology, Medical University of Innsbruck, Innsbruck, Austria
Division of Human Genetics, Medical University of Innsbruck, Innsbruck, Austria.
出版信息
Antimicrob Agents Chemother. 2017 Nov 22;61(12). doi: 10.1128/AAC.00755-17. Print 2017 Dec.
Morphological heterogeneity of cultures was observed during continued cultivation of amphotericin B (AMB)-resistant isolates on drug-free medium. Outgrowth leads to the emergence of multiple sectors that might result from increased growth rates at drug-free conditions. We evaluated the differences in AMB susceptibility and virulence between sector subcultures (ATSec), AMB-resistant (ATR) strains, and AMB-susceptible (ATS) strains. By comparing AMB-resistant (ATR) strains and sector (ATSec) cultures we observed a highly significant reduction of AMB MICs in ATSec (ATR MIC, 2 to 32 μg/ml; ATSec MIC, 0.12 to 5 μg/ml). Furthermore, survival studies revealed an enhanced virulence of ATSec, which was comparable with that of AMB-sensitive strains (median survival rates for ATS isolates, 72 h; for ATSec isolate ATSec, 84 h; for ATR isolates, 144 h). Our findings clearly demonstrate that spontaneous culture degeneration occurs in and, most importantly, crucially impacts drug efficacy and virulence.
在无药培养基上继续培养两性霉素 B（AMB）耐药分离株时，观察到培养物的形态异质性。生长导致出现多个扇区，这可能是由于在无药条件下生长速度增加所致。我们评估了 AMB 敏感性和毒力在扇区亚培养物（ATSec）、AMB 耐药（ATR）株和 AMB 敏感（ATS）株之间的差异。通过比较 AMB 耐药（ATR）株和扇区（ATSec）培养物，我们观察到 ATSec 中的 AMB MIC 显著降低（ATR MIC，2 至 32 μg/ml；ATSec MIC，0.12 至 5 μg/ml）。此外，生存研究表明 ATSec 的毒力增强，与 AMB 敏感株相当（ATS 分离株的中位生存率为 72 小时；ATSec 分离株 ATSec 为 84 小时；ATR 分离株为 144 小时）。我们的研究结果清楚地表明，自发的培养退化在两性霉素 B 耐药中发生，更重要的是，这对药物疗效和毒力有重大影响。
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