Whole Genomic Analysis Revealed High Genetic Diversity and Drug-Resistant Characteristics of Mycobacterium tuberculosis in Guangxi, China

Dabin Liang; Zexuan Song; Xiaoyan Liang; Huifang Qin; Liwen Huang; Jing Ye; Rushu Lan; Dan Luo; Yanlin Zhao; Mei Lin

doi:10.2147/IDR.S410828

Whole Genomic Analysis Revealed High Genetic Diversity and Drug-Resistant Characteristics of Mycobacterium tuberculosis in Guangxi, China

Infect Drug Resist. 2023 Aug 3:16:5021-5031. doi: 10.2147/IDR.S410828. eCollection 2023.

Authors

Dabin Liang^#^{1

2}, Zexuan Song^#³, Xiaoyan Liang^#^{1

2}, Huifang Qin^{1

2}, Liwen Huang^{1

2}, Jing Ye^{1

2}, Rushu Lan⁴, Dan Luo⁵, Yanlin Zhao³, Mei Lin^{1

2}

Affiliations

¹ Guangxi Zhuang Autonomous Region Center for Disease Control and Prevention, Nanning, Guangxi, People's Republic of China.
² Guangxi Key Laboratory of Major Infectious Disease Prevention and Control and Biosafety Emergency Response, Nanning, Guangxi, People's Republic of China.
³ National Tuberculosis Reference Laboratory, Chinese Center for Disease Control and Prevention, Beijing, People's Republic of China.
⁴ Department of Clinical Laboratory, Jiangbin Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, People's Republic of China.
⁵ School of Public Health and Management, Guangxi University of Chinese Medicine, Nanning, Guangxi, People's Republic of China.

^# Contributed equally.

Abstract

Background: Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is a major public health issue in China. Nevertheless, the prevalence and drug resistance characteristics of isolates vary in different regions and provinces. In this study, we investigated the population structure, transmission dynamics and drug-resistant profiles of Mtb in Guangxi, located on the border of China.

Methods: From February 2016 to April 2017, 462 clinical M. tuberculosis isolates were selected from 5 locations in Guangxi. Drug-susceptibility testing was performed using 6 common anti-tuberculosis drugs. The genotypic drug resistance and transmission dynamics were analyzed by the whole genome sequence.

Results: Our data showed that the Mtb in Guangxi has high genetic diversity including Lineage 1 to Lineage 4, and mostly belong to Lineage 2 and Lineage 4. Novelty, 9.6% of Lineage 2 isolates were proto-Beijing genotype (L2.1), which is rare in China. About 12.6% of isolates were phylogenetically clustered and formed into 28 transmission clusters. We observed that the isolates with the high resistant rate of isoniazid (INH, 21.2%), followed by rifampicin (RIF, 13.2%), and 6.7%, 12.1%, 6.7% and 1.9% isolates were resistant to ethambutol (EMB), streptomycin (SM), ofloxacin (OFL) and kanamycin (KAN), respectively. Among these, 6.5% and 3.3% of isolates belong to MDR-TB and Pre-XDR, respectively, with a high drug-resistant burden. Genetic analysis identified the most frequently encountered mutations of INH, RIF, EMB, SM, OFL and KAN were katG_Ser315Thr (62.2%), rpoB_Ser450Leu (42.6%), embB_Met306Vol (45.2%), rpsL_Lys43Arg (53.6%), gyrA_Asp94Gly (29.0%) and rrs_A1401G (66.7%), respectively. Additionally, we discovered that isolates from border cities are more likely to be drug-resistant than isolates from non-border cities.

Conclusion: Our findings provide a deep analysis of the genomic population characteristics and drug-resistant of M. tuberculosis in Guangxi, which could contribute to developing effective TB prevention and control strategies.

Keywords: Mycobacterium tuberculosis; drug-resistance; genetic diversity; tuberculosis; whole genome sequencing.

Grants and funding

This work was supported by grants from Guangxi Medical and health key discipline construction project and National Natural Science Foundation of China (81560549).