The Value of the inhA Mutation Detection in Predicting Ethionamide Resistance Using Melting Curve Technology

Yanhua Song,1 Guirong Wang,2 Qiang Li,1 Rongmei Liu,1 Liping Ma,1 Qi Li,3 Mengqiu Gao1 1Department of Tuberculosis, Beijing Chest Hospital, Capital Medical University, Beijing 101149, People’s Republic of China; 2National Clinical Laboratory on Tuberculosis, Beijing Key Laboratory on Drug-Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing 101149, People’s Republic of China; 3Clinical Center on Tuberculosis, Beijing Chest Hospital, Capital Medical University, Beijing 101149, People’s Republic of ChinaCorrespondence: Qi LiClinical Center on Tuberculosis, Beijing Chest Hospital, Capital Medical University, Beijing 101149, People’s Republic of ChinaTel +86 10 89509322Fax +86 1069546790Email liqi88_dr@163.comMengqiu GaoDepartment of Tuberculosis, Beijing Chest Hospital, Capital Medical University, Beijing 101149, People’s Republic of ChinaTel +86 10 89509322Fax +86 1069546790Email gaomengqi55_dr@163.comObjective: This study aims to analyze the correlation between gene inhA mutations by melting curve technology and phenotypic drug susceptibility (DST) results of ethionamide (ETH), and evaluate whether gene inhA mutations detection can serve as a molecular marker in predicting ETH resistance.Methods: A retrospective analysis was conducted on 382 strains of Mycobacterium tuberculosis (MTB) with the anti-tuberculosis drugs isoniazid (INH), rifampicin (RIF), ETH, and others. Phenotypic drug susceptibility and the results of inhA and katG genotypes (mutation and no mutation) were obtained using the melting curve technology MeltPro TB assay.Results: Of the 382 clinical strains of MTB tested, 118 (30.9%) were resistant to INH, and 28 (7.3%) were resistant to ETH. Among the 28 phenotypically ETH-resistant strains, inhA mutations accounted for 42.9% (12/28). These ETH-resistant strains comprise 35.3% (12/34) of the 34 inhA mutant strains. Of 8 single inhA mutation strains (without katG or rpoB mutation), 4(50%) were resistant to INH; however, all of these 8 strains were sensitive to ETH.Conclusion: The inhA mutation test may not be a reliable predictor of ETH resistance. Mutant inhA strains are not necessarily resistant to ETH. The strains with single inhA mutation (without katG or rpoB mutation) may be effective for ETH treatment. The use of ETH in clinical medicine should be guided by gene (other than inhA alone) detection and phenotypic drug susceptibility testing.Keywords: melting curve technique, Mycobacterium tuberculosis, drug resistance, inhA, gene mutation, prothionamide, ethionamide