Low Prevalence of fks1 Hot Spot 1 Mutations in a Worldwide Collection of Candida Strains
Low Prevalence of fks1 Hot Spot 1 Mutations in a Worldwide Collection of Candida Strains
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DOI：
10.1128/aac.01711-09
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发表时间：
2010-06-01
影响因子：
4.9
通讯作者：
Pfaller, Michael A.
中科院分区：
文献类型：
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作者：
Castanheira, Mariana;Woosley, Leah N.;Pfaller, Michael A.
我们评估了来自6种具有不同caspofunins MIC值（从8 μ g/ml起）的133株念珠菌fks1热点（HS） 1突变的流行率。只有4株（2.9%）菌株出现了FKS1 HS1氨基酸替代，分别是32株白色念珠菌（F641Y） 1株（3.1%）、34株光裂念珠菌（S645P） 1株（2.9%）和12株热带念珠菌（F641S） 2株（16.7%）。显示FKS1 HS1改变的4株分离株显示caspofunin MIC结果升高（1至80 μ g/ml），但在野生型MIC人群中，某些情况下anidulfunin和micafungin MIC值分别降低（0.12至4 μ g/ml和0.25至4 μ g/ml），使用流行病学临界值（ECV）确定。克鲁氏假丝酵母菌、假丝酵母菌和吉列蒙地假丝酵母菌分离株检测显示，无论棘球菌素MIC结果如何，FKS1 HS1均未发生改变。我们还分析了8株白色念珠菌和7株光秃念珠菌fks1和fks2其他HS区域的突变。3株光裂菌在FKS2 HS1上表现出变异（2株S645P， 1株L644W）。总的来说，显示S645P突变的菌株比具有其他突变的菌株具有更高的棘白菌素MIC值。总体而言，在ECV内显示caspofungin MIC值的念珠菌菌株没有显示fks HS突变。相比之下，在该区域发生变化的菌株在野生型群体中显示出anidulafungin和/或micafungin MIC值，这表明caspofungin可能是检测这些抗性突变最敏感的药物。此外，来自大量地理上不同的念珠菌的结果表明，fks1 HS1突变在不同棘白菌素MIC水平的分离株中仍然不常见。
We evaluated the prevalence of fks1 hot spot (HS) 1 mutations among 133 Candida strains from six species displaying various caspofungin MIC values (from 8 mu g/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 mu g/ml) but lower anidulafungin and micafungin MIC values (0.12 to 4 mu g/ml and 0.25 to 4 mu g/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.