JMI Laboratories, North Liberty, IA 52317, USA.
Antimicrob Agents Chemother. 2010 Jun;54(6):2655-9. doi: 10.1128/AAC.01711-09. Epub 2010 Apr 5.
We evaluated the prevalence of fks1 hot spot (HS) 1 mutations among 133 Candida strains from six species displaying various caspofungin MIC values (from < or =0.008 to >8 microg/ml). Only 4 (2.9%) strains displayed FKS1 HS1 amino acid substitutions: 1 C. albicans (F641Y) among 32 isolates tested (3.1%), 1 C. glabrata (S645P) among 34 isolates tested (2.9%), and 2 C. tropicalis (F641S) among 12 isolates tested (16.7%). The 4 isolates displaying FKS1 HS1 alterations showed elevated caspofungin MIC results (1 to >8 microg/ml) but lower anidulafungin and micafungin MIC values (0.12 to 4 microg/ml and 0.25 to 4 microg/ml, respectively) in some instances within the wild-type MIC population, as determined using the epidemiologic cutoff values (ECV). Candida krusei, C. parapsilosis, and C. guilliermondii isolates tested showed no FKS1 HS1 alterations regardless of echinocandin MIC result. We additionally analyzed 8 C. albicans and 7 C. glabrata strains for mutations on other HS regions of fks1 and fks2. Three C. glabrata strains showed alterations on FKS2 HS1 (two S645P and one L644W). In general, strains displaying S645P alteration showed higher echinocandin MIC values than strains harboring other mutations. Overall, Candida spp. strains showing caspofungin MIC values within the ECV did not display fks HS mutations. In contrast, strains showing alterations in this region displayed anidulafungin and/or micafungin MIC values within the wild-type population, suggesting that caspofungin could be the most sensitive agent for detection of these resistance mutations. Furthermore, results from this large, geographically diverse Candida spp. collection demonstrated that fks1 HS1 mutations remain uncommon among isolates with various echinocandin MIC levels.
我们评估了来自六个种属的 133 株念珠菌菌株中 fks1 热点（HS）1 突变的流行率，这些菌株的卡泊芬净 MIC 值（从 <=0.008 至 >8μg/ml）各不相同。仅有 4 株（2.9%）显示 FKS1 HS1 氨基酸取代：32 株受试菌株中的 1 株白念珠菌（F641Y）（3.1%），34 株受试菌株中的 1 株光滑念珠菌（S645P）（2.9%），以及 12 株受试菌株中的 2 株热带念珠菌（F641S）（16.7%）。4 株显示 FKS1 HS1 改变的菌株表现出卡泊芬净 MIC 结果升高（1 至 >8μg/ml），但在野生型 MIC 群体中，某些情况下，安尼芬净和米卡芬净 MIC 值较低（分别为 0.12 至 4μg/ml 和 0.25 至 4μg/ml），这是根据流行病学临界值（ECV）确定的。无论棘白菌素 MIC 结果如何，克柔念珠菌、近平滑念珠菌和季也蒙念珠菌的受试菌株均未显示 FKS1 HS1 改变。我们还分析了 8 株白念珠菌和 7 株光滑念珠菌菌株的其他 fks1 和 fks2 HS 区域的突变。3 株光滑念珠菌菌株显示 FKS2 HS1 改变（2 株 S645P 和 1 株 L644W）。一般来说，显示 S645P 改变的菌株比携带其他突变的菌株显示出棘白菌素 MIC 值更高。总的来说，显示卡泊芬净 MIC 值在 ECV 内的念珠菌属菌株未显示 fks HS 突变。相比之下，在野生型群体中显示该区域改变的菌株显示出安尼芬净和/或米卡芬净 MIC 值，表明卡泊芬净可能是检测这些耐药突变最敏感的药物。此外，来自这个具有地理多样性的大型念珠菌属菌株的结果表明，fks1 HS1 突变在具有各种棘白菌素 MIC 值的菌株中仍然很少见。
