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ORIGINAL RESEARCH article

Front. Cell. Infect. Microbiol.
Sec. Clinical Infectious Diseases
Volume 14 - 2024 | doi: 10.3389/fcimb.2024.1488547
This article is part of the Research Topic Advances in Infectious Disease Research: Tackling Antimicrobial Resistance, Zoonoses, and More View all 3 articles

Whole genome sequencing reveals transmission pattern and drug resistance of Mycobacterium tuberculosis intra-or inter-hosts

Provisionally accepted
Feng Ding Feng Ding 1Wanfei Liu Wanfei Liu 2Wensi Zhang Wensi Zhang 3Chi Wu Chi Wu 3*Shuyan Chen Shuyan Chen 3*Wenjie Lai Wenjie Lai 3*Jiayao Qu Jiayao Qu 3*Qiang Lin Qiang Lin 2Shui-hua Lu Shui-hua Lu 3*Jiuxin Qu Jiuxin Qu 3*
  • 1 National Clinical Research Center for Infectious Diseases, Shenzhen Third People’s Hospital, Shenzhen, China
  • 2 Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen, Guangdong Province, China
  • 3 Second Affiliated Hospital of Southern University of Science and Technology, Shenzhen, Guangdong, China

The final, formatted version of the article will be published soon.

    Background—Tuberculosis (TB) remains a serious global public health problem. The Mycobacterium tuberculosis (MTB) is responsible for approximately 10 million new TB cases globally each year. This study aimed to investigate transmission pattern and drug resistance of MTB in Shenzhen, China. Methods—A retrospective study on 286 samples from 184 TB patients collected between 2015 and 2018 in Shenzhen Third People’s Hospital was conducted using whole genome sequencing. Drug susceptibility testing (DST) was performed using both phenotypic DST (pDST) and molecular DST (mDST). Sample diversity was evaluated by SNPs and transmission clusters were identified based on SNP differences of 12 or fewer in genetic clusters. Results—Except four samples identified as non tuberculous mycobacteria, 282 MTB samples (181 patients) underwent mDST, with 244 samples (162 patients) undergoing pDST. The overall multi-drug resistant rate in patients was 22.31% in pDST (12.00% for new patients and 40.82% for retreatment patients) and 34.48% in mDST (20.41% for new patients and 58.21% for retreatment patients). Totally 92 transmission clusters were identified, encompassing 70.21% samples (57.46% patients), with 5 clusters contained samples (15, 5.32%) from different patients (9, 4.97%), indicating recent transmission. The drug resistant mutations in 36 of 45 transmission clusters (80.00%) were identical in all samples, suggesting the transmission of drug resistance. Patients with multiple samples were categorized into simultaneous sampling (SS) and continuous sampling (CS) groups, revealing significant differences in treatment types, treatment outcomes, residential addresses, and drug resistance types. mDST showed greater accuracy than pDST in SS and CS groups. A novel method based on heterozygous SNPs and Two-sample Kolmogorov-Smirnov test were developed and identified 12 (4.26%) samples as mixed infection samples. 6 of 12 patients had mixed and pure samples together and major strains of mixed samples were closer to corresponding pure strains than minor strains. Conclusions—This retrospective study, conducted at the only municipal hospital specializing in infectious diseases in Shenzhen, provides the opportunity to understand drug resistance of TB patients, which mainly are refractory patients. The study revealed transmission pattern of MTB, analyzed mixed infections, and tracked changes in MTB strains during short/long-term treatment.

    Keywords: Mycobacterium tuberculosis, Transmission pattern, whole genome sequencing, Phenotypic DST, drug resistant mutations

    Received: 30 Aug 2024; Accepted: 20 Dec 2024.

    Copyright: © 2024 Ding, Liu, Zhang, Wu, Chen, Lai, Qu, Lin, Lu and Qu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Chi Wu, Second Affiliated Hospital of Southern University of Science and Technology, Shenzhen, Guangdong, China
    Shuyan Chen, Second Affiliated Hospital of Southern University of Science and Technology, Shenzhen, Guangdong, China
    Wenjie Lai, Second Affiliated Hospital of Southern University of Science and Technology, Shenzhen, Guangdong, China
    Jiayao Qu, Second Affiliated Hospital of Southern University of Science and Technology, Shenzhen, Guangdong, China
    Shui-hua Lu, Second Affiliated Hospital of Southern University of Science and Technology, Shenzhen, Guangdong, China
    Jiuxin Qu, Second Affiliated Hospital of Southern University of Science and Technology, Shenzhen, Guangdong, China

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