Publication date: Aug 01, 2025
Multidrug-resistant tuberculosis (MDR-TB) remains a major public health challenge in China. Hainan, China’s largest tropical island, possesses distinct socio-geographical features. However, the drug resistance patterns and molecular epidemiology of MDR-TB in this region have not been fully elucidated. This study aimed to assess the correlation between drug resistance genotypes and phenotypic resistance levels in multidrug-resistant Mycobacterium tuberculosis (MDR-MTB) strains collected from Hainan Island, using whole-genome sequencing (WGS) and phenotypic drug susceptibility testing (DST). MDR-MTB strains isolated from patients on Hainan Island (2019-2021) were analyzed. Minimum inhibitory concentrations (MIC) for 15 anti-TB drugs were determined by broth microdilution (BMD). Whole-genome sequencing (WGS) was performed using Illumina NovaSeq 6000. Genotypic resistance was predicted via TB-Profiler, and correlations between resistance mutations and MIC levels were assessed. A total of 209 MDR-MTB strains were analyzed. Strains of lineage 2. 2 exhibited significantly higher resistance to ethambutol (EMB) compared to non-lineage 2 strains (P 95%) for second-line injectable aminoglycosides (amikacin [AMK], capreomycin [CPM], and kanamycin [KM]), but sensitivity for other second-line drugs except for fluoroquinolone drug moxifloxacin (MOX, 94. 4%) was below 80. 0%. Notably, mutations in katG_S315T, rpoB_S450L, and gyrA_D94G were strongly associated with high-level resistance, while mutations in fabG1, ahpC, embA promoters, and gyrA at codon 90 were linked to low-level resistance. This study quantitatively demonstrates the relationship between specific drug resistance genotypes and resistance levels. It is the first to characterize the regional resistance spectrum of MDR-MTB strains on Hainan Island. These findings offer a novel foundation for MIC-based dose adjustment and the optimization of treatment strategies in this region. TRIAL REGISTRATION: MR-46-23-020530. Date of registration:2023-07-03.
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Semantics
| Type | Source | Name |
|---|---|---|
| disease | MESH | tuberculosis |
| pathway | KEGG | Tuberculosis |
| disease | MESH | Multidrug-resistant tuberculosis |
| disease | IDO | drug susceptibility |
| drug | DRUGBANK | Dihydrostreptomycin |
| drug | DRUGBANK | Methyl isocyanate |
| drug | DRUGBANK | Ethambutol |
| drug | DRUGBANK | Amikacin |
| drug | DRUGBANK | Capreomycin |
| drug | DRUGBANK | Kanamycin |
| drug | DRUGBANK | Moxifloxacin |
| pathway | REACTOME | Reproduction |
| disease | MESH | Infectious Diseases |
| drug | DRUGBANK | Coenzyme M |
| drug | DRUGBANK | Rifampicin |
| drug | DRUGBANK | Isoniazid |
| disease | IDO | pathogen |
| disease | MESH | treatment failure |
| disease | MESH | relapse |
| disease | IDO | country |
| drug | DRUGBANK | Ilex paraguariensis leaf |
| drug | DRUGBANK | Pyrazinamide |
| drug | DRUGBANK | Protionamide |
| drug | DRUGBANK | Aminosalicylic Acid |
| drug | DRUGBANK | Cycloserine |
| drug | DRUGBANK | Linezolid |
| drug | DRUGBANK | Clofazimine |
| drug | DRUGBANK | Bedaquiline |
| drug | DRUGBANK | Delamanid |
| drug | DRUGBANK | Flunarizine |
| drug | DRUGBANK | Aspartame |
| drug | DRUGBANK | Methylergometrine |
| disease | IDO | assay |
| disease | IDO | quality |