AI Article Synopsis
- This study investigates the molecular characteristics of fluoroquinolone-resistant and multidrug-resistant tuberculosis (TB) strains in Tianjin, China, using whole-genome sequencing to better understand drug resistance.
- Researchers isolated 21 strains from sputum samples and identified mutations in 15 genome regions linked to drug resistance, achieving high sensitivity rates for predicting resistance to various anti-TB drugs compared to traditional testing methods.
- The findings suggest that while genome sequencing effectively predicts drug resistance in most cases, some resistant isolates may employ different mechanisms not explained by the identified mutations.
Article Abstract
Objective: Tuberculosis (TB) caused by remains a global concern. This study aimed to determine the molecular characteristics of fluoroquinolone-resistant and multidrug-resistant strains using whole-genome sequencing to predict drug resistance in in Tianjin, China, which has not been established previously.
Methods: Twenty-one fluoroquinolone-resistant and multidrug-resistant strains were isolated from sputum samples. Phenotypic drug resistance against 12 anti-tuberculosis drugs was determined using drug susceptibility testing. Whole-genome sequencing was performed to predict drug resistance in based on genome regions associated with drug resistance. The sensitivity of whole-genome sequencing for predicting drug resistance was calculated based on phenotypic drug susceptibility testing information.
Results: Among the 21 isolates, mutations in 15 genome regions associated with drug resistance, including for rifampicin; and promoter for isoniazid; and for ofloxacin and moxifloxacin; for streptomycin; for streptomycin, amikacin, kanamycin and capreomycin; and for pyrazinamide; , and for ethambutol; for protionamide; and for para-aminosalicylic acid, were detected. Compared with traditional drug susceptibility testing results, the sensitivities for whole-genome sequencing of rifampin, isoniazid, ofloxacin, moxifloxacin, streptomycin, ethambutol, pyrazinamide, kanamycin, and amikacin resistance were 100%, 90.48%, 95.24%, 92.86%, 95.27%, 85.71%, 66.67%, 50%, and 50%, respectively. The sensitivities for whole-genome sequencing of capreomycin, protionamide, and para-aminosalicylic acid were not calculated because only one isolate showed phenotypic drug resistance. Mutations determined in drug susceptibility-associated genes can explain phenotypic drug resistance in most isolates. Notably, these mutations were absent in certain drug-resistant isolates, indicating other drug resistance mechanisms.
Conclusion: Whole-genome sequencing represents an effective diagnostic tool for fluoroquinolone-resistant and multidrug-resistant TB though it has some obstacles. Whole-genome sequencing should be used to predict drug resistance prior to performing traditional phenotypic drug susceptibility testing in Tianjin, China.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9013706 | PMC |
| http://dx.doi.org/10.2147/IDR.S361635 | DOI Listing |
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