Genetic diversity and transmission pattern of multidrug-resistant tuberculosis based on whole-genome sequencing in Wuhan, China

BackgroundInvestigating the molecular epidemiological characteristics of multidrug-resistant tuberculosis (MDR-TB) in China’s moderate-burden regions, such as Wuhan, is crucial for understanding and controlling disease transmission.Materials and methodsThis study analyzed MDR-TB isolates from pulmon...

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Main Authors: Liqing Wei, Jun Chen, Zhen Deng, Zefang Zhang, Zhengbin Zhang, Qionghong Duan
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-01-01
Series:Frontiers in Public Health
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Online Access:https://www.frontiersin.org/articles/10.3389/fpubh.2025.1442987/full
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author Liqing Wei
Jun Chen
Zhen Deng
Zefang Zhang
Zhengbin Zhang
Qionghong Duan
author_facet Liqing Wei
Jun Chen
Zhen Deng
Zefang Zhang
Zhengbin Zhang
Qionghong Duan
author_sort Liqing Wei
collection DOAJ
description BackgroundInvestigating the molecular epidemiological characteristics of multidrug-resistant tuberculosis (MDR-TB) in China’s moderate-burden regions, such as Wuhan, is crucial for understanding and controlling disease transmission.Materials and methodsThis study analyzed MDR-TB isolates from pulmonary tuberculosis cases registered at Wuhan Pulmonary Hospital in 2017. Whole genome sequencing (WGS) was used to identify resistance-conferring mutations, examine their associations with specific Mycobacterium tuberculosis lineages or sublineages, and assess clustering profiles.ResultsAmong the 149 analyzed strains, the most prevalent mutations associated with resistance to 11 anti-tuberculosis drugs were identified as follows: rpoB Ser450Leu (59.73%, rifampicin), katG Ser315Thr (62.42%, isoniazid), embB Met306Val (42.86%, ethambutol), rpsL Lys43Arg (68.13%, streptomycin), pncA Trp68Arg (10.53%, pyrazinamide), gyrA Asp94Gly (22.50%, fluoroquinolones), and rrs 1401A > G (50.00–100.00%, second-line injectable aminoglycosides). Additional mutations were detected in fabG1 c-15C > T (42.86%, ethionamide) and thyX c-16C > T (21.43%, p-aminosalicylic acid). Notably, rare mutations absent from the WHO mutation catalog, such as ahpC c-52C > T and rpsL Lys43Thr, were also observed. The mutation frequency of embB Met306Ile was significantly higher in Lineage 4 (L4) strains than in Lineage 2 (L2) strains (p = 0.0150), while the rpsL Lys43Arg mutation frequency was lower in L4 compared to L2 (p = 0.0333). A total of 31 MDR MTB Mycobacterium tuberculosis isolates formed clusters, resulting in a clustering rate of 20.81% and a recent transmission rate of 11.41%. The clustering rates between L4 and L2 strains were not significantly different (χ2 = 0.0017, p > 0.05).ConclusionThe genetic diversity of MDR-TB in Wuhan demonstrates unique characteristics, with evidence of localized transmission. These findings highlight the urgent need to strengthen measures to detect early cases of MDR-TB and control transmission of MDR-TB in the region.
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spelling doaj-art-b2f96ee53a7b44978cf0f8f3fdf3b7422025-01-28T06:41:08ZengFrontiers Media S.A.Frontiers in Public Health2296-25652025-01-011310.3389/fpubh.2025.14429871442987Genetic diversity and transmission pattern of multidrug-resistant tuberculosis based on whole-genome sequencing in Wuhan, ChinaLiqing Wei0Jun Chen1Zhen Deng2Zefang Zhang3Zhengbin Zhang4Qionghong Duan5Department of Blood Transfusion, Wuhan Wuchang Hospital, Wuhan University of Science and Technology, Wuhan, ChinaDepartment of Clinical Laboratory, Wuhan Pulmonary Hospital, Wuhan, ChinaDepartment of Clinical Laboratory, Wuhan Pulmonary Hospital, Wuhan, ChinaDepartment of Tuberculosis Prevention and Control, Wuhan Pulmonary Hospital, Wuhan, Hubei, ChinaDepartment of Tuberculosis Prevention and Control, Wuhan Pulmonary Hospital, Wuhan, Hubei, ChinaDepartment of Tuberculosis Prevention and Control, Wuhan Pulmonary Hospital, Wuhan, Hubei, ChinaBackgroundInvestigating the molecular epidemiological characteristics of multidrug-resistant tuberculosis (MDR-TB) in China’s moderate-burden regions, such as Wuhan, is crucial for understanding and controlling disease transmission.Materials and methodsThis study analyzed MDR-TB isolates from pulmonary tuberculosis cases registered at Wuhan Pulmonary Hospital in 2017. Whole genome sequencing (WGS) was used to identify resistance-conferring mutations, examine their associations with specific Mycobacterium tuberculosis lineages or sublineages, and assess clustering profiles.ResultsAmong the 149 analyzed strains, the most prevalent mutations associated with resistance to 11 anti-tuberculosis drugs were identified as follows: rpoB Ser450Leu (59.73%, rifampicin), katG Ser315Thr (62.42%, isoniazid), embB Met306Val (42.86%, ethambutol), rpsL Lys43Arg (68.13%, streptomycin), pncA Trp68Arg (10.53%, pyrazinamide), gyrA Asp94Gly (22.50%, fluoroquinolones), and rrs 1401A > G (50.00–100.00%, second-line injectable aminoglycosides). Additional mutations were detected in fabG1 c-15C > T (42.86%, ethionamide) and thyX c-16C > T (21.43%, p-aminosalicylic acid). Notably, rare mutations absent from the WHO mutation catalog, such as ahpC c-52C > T and rpsL Lys43Thr, were also observed. The mutation frequency of embB Met306Ile was significantly higher in Lineage 4 (L4) strains than in Lineage 2 (L2) strains (p = 0.0150), while the rpsL Lys43Arg mutation frequency was lower in L4 compared to L2 (p = 0.0333). A total of 31 MDR MTB Mycobacterium tuberculosis isolates formed clusters, resulting in a clustering rate of 20.81% and a recent transmission rate of 11.41%. The clustering rates between L4 and L2 strains were not significantly different (χ2 = 0.0017, p > 0.05).ConclusionThe genetic diversity of MDR-TB in Wuhan demonstrates unique characteristics, with evidence of localized transmission. These findings highlight the urgent need to strengthen measures to detect early cases of MDR-TB and control transmission of MDR-TB in the region.https://www.frontiersin.org/articles/10.3389/fpubh.2025.1442987/fullmultidrug-resistant tuberculosiswhole-genome sequencinggenetic diversitytransmission patternWuhanChina
spellingShingle Liqing Wei
Jun Chen
Zhen Deng
Zefang Zhang
Zhengbin Zhang
Qionghong Duan
Genetic diversity and transmission pattern of multidrug-resistant tuberculosis based on whole-genome sequencing in Wuhan, China
Frontiers in Public Health
multidrug-resistant tuberculosis
whole-genome sequencing
genetic diversity
transmission pattern
Wuhan
China
title Genetic diversity and transmission pattern of multidrug-resistant tuberculosis based on whole-genome sequencing in Wuhan, China
title_full Genetic diversity and transmission pattern of multidrug-resistant tuberculosis based on whole-genome sequencing in Wuhan, China
title_fullStr Genetic diversity and transmission pattern of multidrug-resistant tuberculosis based on whole-genome sequencing in Wuhan, China
title_full_unstemmed Genetic diversity and transmission pattern of multidrug-resistant tuberculosis based on whole-genome sequencing in Wuhan, China
title_short Genetic diversity and transmission pattern of multidrug-resistant tuberculosis based on whole-genome sequencing in Wuhan, China
title_sort genetic diversity and transmission pattern of multidrug resistant tuberculosis based on whole genome sequencing in wuhan china
topic multidrug-resistant tuberculosis
whole-genome sequencing
genetic diversity
transmission pattern
Wuhan
China
url https://www.frontiersin.org/articles/10.3389/fpubh.2025.1442987/full
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