Characterization of Fluoroquinolone-Resistant and Multidrug-Resistant Isolates Using Whole-Genome Sequencing in Tianjin, China.

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.