Mutation EthAW21R confers co-resistance to protionamide and ethionamide in both Mycobacterium bovis BCG and Mycobacterium tuberculosis H37Rv

Julius Mugweru; Jianxiong Liu; Gaelle Makafe; Gift Chiwala; Bangxing Wang; Changwei Wang; Xinjie Li; Yaoju Tan; Wing Wai Yew; Shouyong Tan; Tianyu Zhang

doi:10.2147/IDR.S163965

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Mutation EthA_W21R confers co-resistance to protionamide and ethionamide in both Mycobacterium bovis BCG and Mycobacterium tuberculosis H37Rv

Authors Mugweru J, Liu J, Makafe G, Chiwala G , Wang B, Wang C, Li X, Tan Y, Yew WW, Tan S , Zhang T

Received 28 January 2018

Accepted for publication 20 March 2018

Published 13 June 2018 Volume 2018:11 Pages 891—894

DOI https://doi.org/10.2147/IDR.S163965

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Joachim Wink

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Julius Mugweru,^1–3,* Jianxiong Liu,^4,* Gaelle Makafe,^1,2 Gift Chiwala,^1,2 Bangxing Wang,¹ Changwei Wang,¹ Xinjie Li,⁴ Yaoju Tan,⁴ Wing Wai Yew,⁵ Shouyong Tan,⁴ Tianyu Zhang^1,2

¹State Key Laboratory of Respiratory Disease, Guangzhou Regenerative Medicine and Health Guangdong Laboratory (GRMH-GDL), Guangzhou Institutes of Biomedicine and Health (GIBH), Chinese Academy of Sciences (CAS), Guangzhou, China; ²University of Chinese Academy of Sciences, Beijing, China; ³Department of Biological Sciences, University of Embu, Embu, Kenya; ⁴State Key Laboratory of Respiratory Disease, Department of Clinical Laboratory, Guangzhou Chest Hospital, Guangzhou, ⁵Stanley Ho Centre for Emerging Infectious Diseases, The Chinese University of Hong Kong, Hong Kong, China

*These authors contributed equally to this work

Abstract: Ethionamide (ETA) and prothionamide (PRO) are interchangeably used in tuberculosis (TB) chemotherapy regimens. Subtle discrepancies between biochemical and genetic information on the modes of sensitivity and resistance of isoniazid (INH) and ETA warrants further studies. We report a new mutation – EthA_W21R – in Mycobacterium bovis Bacillus Calmette-Guérin that corresponds with co-resistance to both PRO and ETA, which to the best of our knowledge has not been reported before. Our findings suggest that mutation EthA_W21R could be used as a marker site for testing PRO and ETA cross-resistance.

Keywords: mutation, EthA_W21R, isoniazid, co-resistance, thioamides, molecular marker

Acknowledgments

This work was supported by the National Mega project of China for Innovative Drugs (2018ZX09721001-003-003) and for Main Infectious Diseases (2017ZX10302301-003-002), the National Natural Science Foundation of China (81572037), the Chinese Academy of Sciences Grants (154144KYSB20150045, KFZD-SW-207, and YJKYYQ20170036) and Guangzhou Municipal Industry and Research Collaborative Innovation Program (201508020248 and 201604020019). It was also partially supported by the Public Research and Capacity Building Project of Guangdong Province (2017A020212004), the Guangzhou Municipal Clinical Medical Centre Program (155700012) and the Key Project Grant (SKLRD2016ZJ003) from the State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Diseases, First Affiliated Hospital of Guangzhou Medical University. TZ received support from Science and Technology Innovation Leader of Guangdong Province (2016TX03R095). JM is a recipient of the University of Chinese Academy of Sciences PhD Fellowship Program while GM and GC are recipients of the CAS-TWAS President’s PhD Fellowship Program for International Students. The work was undertaken at the following institutes, which are mandated to undertake tuberculosis studies in Southern China: 1) State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China, and 2) State Key Laboratory of Respiratory Disease, Department of Clinical Laboratory, Guangzhou Chest Hospital, Guangzhou, China. The facilities are compliant with biosafety level 2+ and 3 requirements for handling infectious materials.

Disclosure

The authors report no conflicts of interest in this work.

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