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A Profile of Drug-Resistant Mutations in Mycobacterium tuberculosis Isolates from Guangdong Province, China

  • ORIGINAL RESEARCH ARTICLE
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Abstract

Guangdong Province, China’s largest economy, has a high incidence of tuberculosis (TB). At present, there are few reports on the distribution, transmission and drug resistance of Mycobacterium tuberculosis (Mtb) strains in this region. In this study, we performed minimum inhibitory concentration testing for 14 anti-TB drugs and whole-genome sequencing of 713 clinical Mtb isolates from 20,662 sputum culture-positive tuberculosis patients registered at 31 tuberculosis drug resistance surveillance sites covering 20 cities in Guangdong Province from 2016 to 2018. Moreover, we evaluated genome-wide associations between mutations and drug resistance, and further investigated the differences in the MICs of mutations. The epidemiology, drug-resistant phenotypes and whole genome sequencing data of 713 clinical Mtb isolates were analyzed, revealing the lineage distribution and drug-resistant gene profiles in Guangdong Province. WGS combined with quantitative MIC measurements identified several novel loci associated with resistance, of which 16 loci were found to be related to resistance to more than one drug. This study analyzed the lineage distribution, prevalence characteristics and resistance-corresponding gene profiles of Mtb isolates in Guangdong province, and provided a theoretical basis for the formulation of tuberculosis prevention and control policy in the province.

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Availability of Data and Materials

The raw data of WGS has already been submitted to the Sequence Read Archive (SRA) database. The BioProject accession numbers are PRJNA866200.

Abbreviations

TB:

Tuberculosis

Mtb:

Mycobacterium tuberculosis

MDR/RR–TB:

Isoniazid and rifampicin TB or rifampicin-resistant TB

WGS:

Whole-genome sequencing

MIC:

Minimum inhibitory concentration

INH:

Isoniazid

RIF:

Rifampicin

SM:

Streptomycin

PZA:

Pyrazinamide

EMB:

Ethambutol

OFX:

Ofloxacin

RBU:

Rifabutin

MFX:

Moxifloxacin

PAS:

Para-aminosalicylic acid

LFX:

Levofloxacin

CAP:

Capreomycin

AKM:

Amikacin

KM:

Kanamycin

PTO:

Prothionamide

ETH:

Ethionamide

GWAS:

Genome-wide association study

QQ:

Quantile-quantile

LJ:

Löwenstein–Jensen

NTM:

Non-tuberculosis mycobacteria

DST:

Drug susceptibility testing

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Acknowledgements

The authors thank the partners of TB drug resistance monitoring stations in Guangdong province for their hard work in sorting out patient information and collecting Mtb strains. The authors thank Tao Chen, Zhenyan Li and Li Yu, formerly working in Center for Tuberculosis Control of Guangdong Province, for their hard work in the establishment of biobank. The authors express appreciation of Zhichao Chen from Shanghai Gene-Optimal Science &Technology Co., Ltd for help with WGS analysis.

Funding

This work was supported by a Major Infectious Disease Prevention and Control of the National Science and Technique Major Project [2018ZX10715004], the Science and Technology Planning Project of Guangzhou [202201010785] and Medical Science Foundation of Guangdong Province [B2021012].

Author information

Author notes

  1. Qi Sun

    Present address: Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China

  2. Chenchen Zhang, Zhuhua Wu, Xinchun Huang, and Yuchuan Zhao have contributed equally to this work.

Authors and Affiliations

  1. Center for Tuberculosis Control of Guangdong Province, Guangzhou, 510630, China

    Chenchen Zhang, Zhuhua Wu, Xinchun Huang, Yuchuan Zhao, Qi Sun, Yanmei Chen, Huixin Guo, Qinghua Liao, Huizhong Wu, Xunxun Chen, Anqi Liang, Meiling Yu, Yuhui Chen & Wenjing Wei

  2. College of Basic Medicine and Public Hygiene, Jinan University, Guangzhou, 510632, China

    Wenjing Wei

  3. Department of Clinical Laboratory, Guangdong Women and Children Hospital, Guangzhou, 511443, China

    Wenya Dong

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Contributions

Wenjing Wei, Yuhui Chen and Meiling Yu conceived the study. Wenjing Wei and Yuhui Chen acquired funding, supervised and administered the project. Chenchen Zhang, Zhuhua Wu, Xinchun Huang, Yuchuan Zhao, Meiling Yu and Qi Sun processed the samples and performed the experiments. Chenchen Zhang, Meiling Yu, Yanmei Chen, Qi Sun, Huixin Guo and Wenya Dong were responsible for collecting clinical strains and conducting drug susceptibility tests. Chenchen Zhang, Yuchuan Zhao and Wenjing Wei analyzed the data. Qinghua Liao, Huizhong Wu and Xunxun Chen were responsible for providing guidance on clinical TB drug use. Anqi Liang and Wenya Dong were responsible for clinical strain information collection and collation. Chenchen Zhang, Wenjing Wei and Yuhui Chen prepared the manuscript. All the authors have read the final version of the manuscript and have approved it.

Corresponding authors

Correspondence to Meiling Yu, Yuhui Chen or Wenjing Wei.

Ethics declarations

Coonflict of interests

The authors declare no competing interests.

Ethics Approval and Consent to Participate

The clinical Mtb isolates used in this study were collected from the Major Infectious Disease Prevention and Control of the National Science and Technique Major Project and preserved by the Biobank of Center for Tuberculosis Control of Guangdong Province. Written informed consent was also obtained from each patient in face-to-face interviews by trained clinicians. The study was performed in accordance with the Declaration of Helsinki and approved by the Medical Ethics Committee of Center for Tuberculosis Control of Guangdong Province, China.

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Zhang, C., Wu, Z., Huang, X. et al. A Profile of Drug-Resistant Mutations in Mycobacterium tuberculosis Isolates from Guangdong Province, China. Indian J Microbiol (2024). https://doi.org/10.1007/s12088-024-01236-3

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