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报告耐多药结核分枝杆菌疑似病例中吡嗪酰胺耐药的 pncA 基因突变。

pncA gene mutations in reporting pyrazinamide resistance among the MDR-TB suspects.

机构信息

Central Laboratory, Nanjing Chest Hospital, Medicine School of Southeast University, Nanjing, Jiangsu, China.

Department of Chronic Communicable Disease, Center for Disease Control and Prevention of Jiangsu Province, Nanjing, China.

出版信息

Infect Genet Evol. 2019 Aug;72:147-150. doi: 10.1016/j.meegid.2018.11.012. Epub 2018 Nov 14.

Abstract

Mutations in pncA gene contributing to PZA resistance was not clearly elucidated in China. To reveal the correlated mutations of pncA gene on pyrazinamide (PZA) resistance. 148 Mycobacterium tuberculosis clinical isolates were included from multi-drug resistant tuberculosis suspects. The MGIT 960 test and microscopic observation drug susceptibility (MODS) assay were adopted for PZA phenotype drug susceptibility test. 120 isolates with consistent MGIT 960 and MODS results were selected for pncA gene sequencing. 68 samples (56.7%) were resistant to PZA while leaving 52 PZA susceptible samples. Out of the 68 PZA resistant isolates, 49 (72.1%) harbored mutations of pncA, and 4 (7.7%) of the 52 PZA susceptible samples harbored mutations of pncA as well. Compared to the phenotype drug resistant pattern of PZA, the mutations of pncA gene reached a sensitivity of 0.72 to report PZA resistance and a specificity of 0.92 to predict PZA susceptibility. Those mutations, Gln10Pro, Asp12Ala, Tyr41Stop, Gly97Asp, Val128Gly and FSC131(ins) exceeding 5% of the total PZA resistant isolates of each, might be helpful but not adequate in PZA molecular susceptibility test design and development.

摘要

在中国,导致吡嗪酰胺(PZA)耐药的 pncA 基因突变尚不清楚。为了揭示 pncA 基因与吡嗪酰胺耐药相关的突变。从耐多药结核病疑似患者中纳入了 148 株结核分枝杆菌临床分离株。采用 MGIT 960 试验和微量观察药物敏感性(MODS)试验进行吡嗪酰胺表型药物敏感性试验。选择 120 株与 MGIT 960 和 MODS 结果一致的分离株进行 pncA 基因测序。68 株(56.7%)对 PZA 耐药,52 株 PZA 敏感。在 68 株 PZA 耐药分离株中,49 株(72.1%)携带 pncA 基因突变,52 株 PZA 敏感分离株中有 4 株(7.7%)携带 pncA 基因突变。与 PZA 表型耐药模式相比,pncA 基因突变对报告 PZA 耐药的灵敏度为 0.72,对预测 PZA 敏感性的特异性为 0.92。这些突变,包括 Gln10Pro、Asp12Ala、Tyr41Stop、Gly97Asp、Val128Gly 和 FSC131(ins),在每个 PZA 耐药分离株中超过 5%,可能有助于,但不足以用于吡嗪酰胺分子药敏试验的设计和开发。

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