Differential Aspergillus lentulus Echinocandin Susceptibilities Are Fksp Independent
Differential Aspergillus lentulus Echinocandin Susceptibilities Are Fksp Independent
复制标题
迟缓曲霉棘白菌素敏感性差异与 Fksp 无关
DOI：
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发表时间：
2010
影响因子：
4.9
通讯作者：
K. Marr
中科院分区：
文献类型：
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作者：
J. Staab;J. N. Kahn;K. Marr
摘要最近报道的香菇曲霉在体外对棘球菌素和其他抗真菌药物表现出不同的敏感性和降低的敏感性。总体而言，香菇分离株对卡泊芬净的敏感性较低，尽管它们对阿尼达芬净和米卡芬净保持敏感性。编码β-1，3-葡聚糖合成酶催化亚单位的基因fks的突变或多态已知会降低念珠菌对棘球菌素的敏感性。和烟曲霉。对香菇FKS序列的分析没有发现该基因的任何已知热点区域存在多态。卡泊芬净和米卡芬净对香菇葡聚糖合成酶的动力学抑制谱与敏感的烟曲霉酶相似。虽然香菇细胞壁甲壳素水平平均为烟曲霉菌的60%，但棘球菌素处理促进了两种生物细胞壁甲壳素含量的增加，表明香菇表现出与烟曲霉菌相似的代偿性甲壳素反应。这些数据表明，香菇对棘球蛋白的不同敏感性与棘球蛋白靶标Fksp无关，并强调了药物在细胞水平上抑制靶酶的能力不同的可能性。
ABSTRACT The recently described species Aspergillus lentulus exhibits differential and reduced susceptibilities to echinocandins and other antifungal drugs in vitro. A. lentulus isolates overall are less susceptible to caspofungin, although they maintain susceptibility to anidulafungin and micafungin. Mutations or polymorphisms in fks, the gene encoding the catalytic subunit of β-1,3-glucan synthase, are known to confer decreased susceptibility to echinocandins in Candida spp. and Aspergillus fumigatus. The analysis of the A. lentulus fks sequence did not reveal a polymorphism at any of the known hot-spot regions of the gene. Caspofungin and micafungin kinetic inhibition profiles of the A. lentulus glucan synthase were comparable to those from susceptible A. fumigatus enzymes. Although the basal cell wall chitin levels in A. lentulus averaged 60% of those in A. fumigatus, echinocandin treatment promoted the increase of cell wall chitin in both organisms, indicating that A. lentulus displays a compensatory chitin response similar to that of A. fumigatus. The data suggest that differential echinocandin susceptibilities in A. lentulus are independent of the echinocandin target, Fksp, and they emphasize the potential that the drugs' capacity to inhibit the target enzyme is unequal at the cellular level.