当前位置: X-MOL 学术Genes › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Point Mutations in the 14-α Sterol Demethylase Cyp51A or Cyp51C Could Contribute to Azole Resistance in Aspergillus flavus
Genes ( IF 3.5 ) Pub Date : 2020-10-17 , DOI: 10.3390/genes11101217
Jose Lucio 1 , Irene Gonzalez-Jimenez 1 , Olga Rivero-Menendez 1 , Ana Alastruey-Izquierdo 1, 2 , Teresa Pelaez 3 , Laura Alcazar-Fuoli 1, 2 , Emilia Mellado 1, 2
Affiliation  

Infections caused by Aspergillus species are being increasingly reported. Aspergillus flavus is the second most common species within this genus causing invasive infections in humans, and isolates showing azole resistance have been recently described. A. flavus has three cyp51-related genes (cyp51A, cyp51B, and cyp51C) encoding 14-α sterol demethylase-like enzymes which are the target of azole drugs. In order to study triazole drug resistance in A. flavus, three strains showing reduced azole susceptibility and 17 azole susceptible isolates were compared. The three cyp51-related genes were amplified and sequenced. A comparison of the deduced Cyp51A, Cyp51B, and Cyp51C protein sequences with other protein sequences from orthologous genes in different filamentous fungi led to a protein identity that ranged from 50% to 80%. Cyp51A and Cyp51C presented several synonymous and non-synonymous point mutations among both susceptible and non-susceptible strains. However, two amino acid mutations were present only in two resistant isolates: one strain harbored a P214L substitution in Cyp51A, and another a H349R in Cyp51C that also showed an increase of cyp51A and cyp51C gene expression compared to the susceptible strain ATCC2004304. Isolates that showed reduced in vitro susceptibility to clinical azoles exhibited a different susceptibility profile to demethylation inhibitors (DMIs). Although P214L substitution might contribute to azole resistance, the role of H349R substitution together with changes in gene expression remains unclear.

中文翻译:

14-α 甾醇脱甲基酶 Cyp51A 或 Cyp51C 中的点突变可能导致黄曲霉中的唑抗性

越来越多地报道了由曲霉属物种引起的感染。黄曲霉是该属中第二大最常见的引起人类侵袭性感染的物种,最近描述了对唑类耐药的分离株。A. flavus 具有三个 cyp51 相关基因(cyp51A、cyp51B 和 cyp51C),编码 14-α 甾醇脱甲基酶样酶,这些酶是唑类药物的靶标。为了研究黄曲霉对三唑类药物的耐药性,比较了三种唑类药物敏感性降低的菌株和 17 种唑类药物敏感性分离株。对三个 cyp51 相关基因进行了扩增和测序。将推导的 Cyp51A、Cyp51B 和 Cyp51C 蛋白质序列与来自不同丝状真菌中直系同源基因的其他蛋白质序列进行比较,导致蛋白质同一性在 50% 到 80% 之间。Cyp51A 和 Cyp51C 在易感和非易感菌株中呈现出几个同义和非同义点突变。然而,两个氨基酸突变仅存在于两个抗性分离株中:一个菌株在 Cyp51A 中具有 P214L 取代,另一个在 Cyp51C 中具有 H349R,与易感菌株 ATCC2004304 相比,Cyp51A 和 cyp51C 基因表达也增加。对临床唑类的体外敏感性降低的分离株对去甲基化抑制剂 (DMIs) 表现出不同的敏感性。尽管 P214L 替代可能导致唑类抗性,但 H349R 替代与基因表达变化的作用仍不清楚。两个氨基酸突变仅存在于两个抗性分离株中:一个菌株在 Cyp51A 中具有 P214L 取代,另一个在 Cyp51C 中具有 H349R,与易感菌株 ATCC2004304 相比,Cyp51A 和 cyp51C 基因表达也增加。对临床唑类的体外敏感性降低的分离株对去甲基化抑制剂 (DMIs) 表现出不同的敏感性。尽管 P214L 替代可能导致唑类抗性,但 H349R 替代与基因表达变化的作用仍不清楚。两个氨基酸突变仅存在于两个抗性分离株中:一个菌株在 Cyp51A 中具有 P214L 取代,另一个在 Cyp51C 中具有 H349R,与易感菌株 ATCC2004304 相比,Cyp51A 和 cyp51C 基因表达也增加。对临床唑类的体外敏感性降低的分离株对去甲基化抑制剂 (DMIs) 表现出不同的敏感性。尽管 P214L 替代可能导致唑类抗性,但 H349R 替代与基因表达变化的作用仍不清楚。对临床唑类的体外敏感性降低的分离株对去甲基化抑制剂 (DMIs) 表现出不同的敏感性。尽管 P214L 替代可能导致唑类抗性,但 H349R 替代与基因表达变化的作用仍不清楚。对临床唑类的体外敏感性降低的分离株对去甲基化抑制剂 (DMIs) 表现出不同的敏感性。尽管 P214L 替代可能导致唑类抗性,但 H349R 替代与基因表达变化的作用仍不清楚。
更新日期:2020-10-17
down
wechat
bug