4.6 Article

Analysis on Drug-Resistance-Associated Mutations among Multidrug-Resistant Mycobacterium tuberculosis Isolates in China

Journal

ANTIBIOTICS-BASEL
Volume 10, Issue 11, Pages -

Publisher

MDPI
DOI: 10.3390/antibiotics10111367

Keywords

Mycobacterium tuberculosis; drug-susceptibility testing; multidrug resistance; mutation

Funding

  1. National Natural Science Foundation [81871691]
  2. Beijing Municipal Natural Science Foundation [21JG0034]
  3. Key Clinical Specialty Project from Beijing Municipal Science & Technology Commission [Z181100001718181]

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The study found the emergence of multidrug-resistant isolates of Mycobacterium tuberculosis in China, with mutations in six resistant genes showing different characteristics among isolates. Specific mutations in certain genes were found to potentially lead to high levels of drug resistance. Therefore, it is necessary to conduct more epidemiological investigations to support the development of rapid detection technologies for drug-resistant tuberculosis.
As the causative bacteria of tuberculosis, Mycobacterium tuberculosis (M. tb) is aggravated by the emergence of its multidrug-resistant isolates in China. Mutations of six of the most frequently reported resistant genes (rpoB, katG, inhA, embB, gyrA, and rpsL) were detected for rifampicin (RIF), isoniazid (INH), ethambutol (EMB), ofloxacin (OFX), and streptomycin (STR) in this study. The amino acid missense mutations (MMs) and their corresponding single nucleotide polymorphism mutations for all drug-resistant (DR) isolates are described in detail. All isolates were divided into non-extensively drug-resistant (Non-XDR) and preXDR/XDR groups. No statistical differences were detected among MMs and linked MMs (LMs) between the two groups, except for rpsL 88 (p = 0.037). In the preXDR/XDR group, the occurrence of MMs in rpoB, katG, and inhA developed phenotypic resistance and MMs of rpoB 531, katG 315, rpsL 43, and rpsL 88 could develop high levels of DR. It is necessary to carry out epidemiological investigations of DR gene mutations in the local region, and thus provide necessary data to support the design of new technologies for rapid detection of resistant M. tb and the optimization of detection targets.

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