Division of Hygiene and Medical Microbiology, Medical University of Innsbruck, Innsbruck, Austria
Division of Human Genetics, Medical University of Innsbruck, Innsbruck, Austria.
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。
