Background: Multidrug-resistant tuberculosis (MDR-TB) has become a great threat to TB control around the world. In 2017, there were 889,000 new tuberculosis cases in China, and 31.1% were MDR/RR-TB (TB resistant to rifampicin). This study aims to explore the the molecular characteristics and factors associated with infection among different genotype MDR strains in Chongqing, China.
Methods: All the 230 MDR-TB isolates were genotyped using 24-loci mycobacterial interspersed repetitive unite variable number tandem repeat (MIRU-VNTR) method and multiplex real-time PCR melting curve assay of Rv2952 gene and mutT2 gene. Polymorphism and clustering analysis of each locus was carried out by BioNumerics Version 5.0.
Results: By genotyping, 83.0% (191/230) of the MDR-TB isolates were Beijing strains, among which 41.9% from the ancient Beijing genotype and 58.1% from the modern Beijing genotype. Based on 24-loci, the 230 MDR isolates were classified into 208 genotypes, among which 38 isolates belonged to 16 clusters. The clustering rate was 16.5%. The percentages of SM-resistant and EMB-resistant in Beijing genotype were significantly higher than those in non-Beijing genotype (P < 0.01). The Beijing genotype had a significantly high risk to be clustered than non-Beijing genotype (p < 0.01). The percentages of SM-resistant isolates in clustered group were significantly higher than non-clustered group (P < 0.01). According to 24-loci, the HGDI was 0.9988, and five loci (Qub11b, Qub26, Mtub21, MIRU26, Mtub04) have high discriminatory power (HGDI > 0.6), while 7 loci (MIRU4, MIRU23, Mtub34, MIRU20, Mtub29, MIRU2, MIRU24) showed negligible diversity (HGDI < 0.1). The percentage of clustered rate showed no difference between 24-loci and 15-loci (p = 0.19).
Conclusion: Among MDR isolates in Chongqing China, Beijing genotype is more likely to be drug resistant and clustered, and SM-resistant isolates are more likely to be clustered that may related to the MDR epidemic. Although 24-loci had a high resolution of genotype, some new loci should be found to replace the poor diversity loci in 24-loci and additional analysis of specific sublineage of Beijing genotype is needed in order to better understand the relations between the molecular characteristics of strains and MDR-TB epidemic.