3 years ago

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

Xiaoyuan Wu, Wei Lu, Yan Shao, Honghuan Song, Guoli Li, Yan Li, Limei Zhu, Cheng Chen

Publication date: Available online 14 November 2018

Source: Infection, Genetics and Evolution

Author(s): Xiaoyuan Wu, Wei Lu, Yan Shao, Honghuan Song, Guoli Li, Yan Li, Limei Zhu, Cheng Chen

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.

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