Drug Sensitivity and Resistance Mechanism in Aspergillus Section Nigri Strains from Japan
Drug Sensitivity and Resistance Mechanism in Aspergillus Section Nigri Strains from Japan
复制标题
DOI：
10.1128/aac.02583-16
复制
发表时间：
2017-08-01
影响因子：
4.9
通讯作者：
Kamei, Katsuhiko
中科院分区：
文献类型：
--
作者：
Hashimoto, Aki;Hagiwara, Daisuke;Kamei, Katsuhiko
尼日尔及其相关种，称为黑曲霉组，广泛分布于地球仪，并且经常从临床标本中分离。在日本，黑曲霉是继烟曲霉之后第二常见的从临床标本中分离的曲霉。我们通过部分β-微管蛋白基因的DNA测序确定了在日本分离的黑曲霉属的种，并通过CLSI M38-A2方法研究了药物敏感性。收集包含20个尼日尔曲霉，59个魏氏曲霉和39个塔宾曲霉菌株。药敏试验显示30 ~ 55%的A.尼日尔，为6.8 ~ 18.6%。welwitschiae和A.根据提出的塔宾曲霉流行病学临界值（ECVs），塔宾曲霉菌株对伊曲康唑（ITC）和/或伏立康唑（VRC）的敏感性较低（所谓耐药）。尼日尔此前ITC和VRC的MIC分布在临床分离株和环境分离株之间无显著差异。当cyp 51 A序列在敏感株和耐药株之间比较时，18个氨基酸突变是A.尼日尔和A. tubingensis;然而，没有一个被证实与唑类耐药相关。三个无关的A。welwitschiae分离物具有cyp 51 A的部分缺失，可能归因于比其它分离物更敏感于唑类。五种抗ITC的A. tubingensis分离株比敏感株表现出更高的cyp 51 A表达。我们的研究结果表明，cyp 51 A点突变可能与唑类耐药无关，但在某些情况下，cyp 51 A的过度表达可能导致这些物种的唑类耐药。
Aspergillus niger and its related species, known as Aspergillus section Nigri, are ubiquitously distributed across the globe and are often isolated from clinical specimens. In Japan, Aspergillus section Nigri is second most often isolated from clinical specimens following Aspergillus fumigatus. We determined the species of Aspergillus section Nigri isolated in Japan by DNA sequencing of partial beta-tubulin genes and investigated drug susceptibility by the CLSI M38-A2 method. The collection contained 20 Aspergillus niger, 59 Aspergillus welwitschiae, and 39 Aspergillus tubingensis strains. Drug susceptibility testing revealed 30 to 55% of A. niger, 6.8 to 18.6% of A. welwitschiae, and 79.5 to 89.7% of A. tubingensis isolates to be less susceptible (so-called resistant) to itraconazole (ITC) and/or voriconazole (VRC) according to the epidemiologic cutoff values (ECVs) proposed for A. niger previously. MIC distributions of ITC or VRC showed no remarkable differences between clinical and environmental isolates. When the cyp51A sequences were compared between susceptible and resistant strains, 18 amino acid mutations were specific for resistant isolates of A. niger and A. tubingensis; however, none of them were confirmed to be associated with azole resistance. Three nonrelated A. welwitschiae isolates possessed a partial deletion in cyp51A, likely attributable to being more susceptible to azoles than other isolates. One of five ITC-resistant A. tubingensis isolates showed higher expression of cyp51A than did susceptible strains. Our results show that cyp51A point mutations may have no association with azole resistance but that in some cases the overexpression of cyp51A may lead to the azole resistance in these species.