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日本曲霉属菌株的药物敏感性及耐药机制

Drug Sensitivity and Resistance Mechanism in Aspergillus Section Strains from Japan.

作者信息

Hashimoto Aki, Hagiwara Daisuke, Watanabe Akira, Yahiro Maki, Yikelamu Alimu, Yaguchi Takashi, Kamei Katsuhiko

机构信息

Division of Clinical Research, Medical Mycology Research Center, Chiba University, Chiba, Japan.

Division of Clinical Research, Medical Mycology Research Center, Chiba University, Chiba, Japan

出版信息

Antimicrob Agents Chemother. 2017 Jul 25;61(8). doi: 10.1128/AAC.02583-16. Print 2017 Aug.

Abstract

and its related species, known as section , are ubiquitously distributed across the globe and are often isolated from clinical specimens. In Japan, section is second most often isolated from clinical specimens following We determined the species of section isolated in Japan by DNA sequencing of partial β-tubulin genes and investigated drug susceptibility by the CLSI M38-A2 method. The collection contained 20 , 59 , and 39 strains. Drug susceptibility testing revealed 30 to 55% of , 6.8 to 18.6% of , and 79.5 to 89.7% of isolates to be less susceptible (so-called resistant) to itraconazole (ITC) and/or voriconazole (VRC) according to the epidemiologic cutoff values (ECVs) proposed for previously. MIC distributions of ITC or VRC showed no remarkable differences between clinical and environmental isolates. When the sequences were compared between susceptible and resistant strains, 18 amino acid mutations were specific for resistant isolates of and ; however, none of them were confirmed to be associated with azole resistance. Three nonrelated isolates possessed a partial deletion in , likely attributable to being more susceptible to azoles than other isolates. One of five ITC-resistant isolates showed higher expression of than did susceptible strains. Our results show that point mutations may have no association with azole resistance but that in some cases the overexpression of may lead to the azole resistance in these species.

摘要

及其相关菌种,即 组,在全球广泛分布,且常常从临床标本中分离得到。在日本, 组是继 之后第二常从临床标本中分离出的菌种。我们通过对部分β-微管蛋白基因进行DNA测序确定了在日本分离出的 组菌种,并采用CLSI M38-A2方法研究了药物敏感性。该菌株集合包含20株 、59株 和39株 菌株。药敏试验显示,根据之前针对 提出的流行病学临界值(ECV),30%至55%的 、6.8%至18.6%的 以及79.5%至89.7%的 分离株对伊曲康唑(ITC)和/或伏立康唑(VRC)敏感性较低(即所谓耐药)。ITC或VRC的MIC分布在临床分离株和环境分离株之间未显示出显著差异。当比较敏感和耐药菌株之间的 序列时,18个氨基酸突变是 和 耐药分离株所特有的;然而,它们均未被证实与唑类耐药相关。三株不相关的 分离株在 中存在部分缺失,这可能归因于它们比其他分离株对唑类更敏感。五株ITC耐药的 分离株中有一株显示出比敏感菌株更高的 表达。我们的结果表明, 点突变可能与唑类耐药无关,但在某些情况下, 的过表达可能导致这些菌种出现唑类耐药。

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