Abstract
Multidrug-resistant Mycobacterium tuberculosis (MDR-TB) is a severe health threat to human beings; however, the epidemic and molecular characteristics exist along with the change in the geographic environment and genealogy. Jiangxi province is located in southeast China, which is a high-MDR-TB burden area. Rifampin (RIF) and isoniazid (INH) are the most important first-line anti-tuberculosis drugs. The major drug target genes include rpoB for RIF and katG, inhA, and ahpC for INH. To determine the frequency and distribution of mycobacterial mutations in these genes, we sequenced specific genes of M. tuberculosis that are associated with resistance to RIF and INH in 157 phenotypic MDR isolates. At the same time, RD105 DTM-PCR and 15 loci MIRU-VNTR were performed to demonstrate the genetic lineage. It was shown that the Beijing genotype was predominant (84.1%) among these strains. The results also showed mutations within the 81 bp core region of rpoB in 93.6% of strains and mutations in a structural gene (katG) and two regulatory regions (the promoter of inhA and intergenic region of oxyR-ahpC) were shown in 88.5% of phenotypic MDR isolates. There were no significant differences in codon mutations between the Beijing and non-Beijing genotypes, as well as the clustered and no-clustered strains. The most prevalent mutations involved in RIF and INH were Ser531Leu in rpoB (55.4%) and Ser315Thr in KatG (56.1%), respectively. There was no significant difference in RIF and INH resistance between MDR-TB and other drug-resistant tuberculosis (DR-TB). The results demonstrated that some MDR-TB patients are predicted to have recent transmission.
Highlights
Tuberculosis (TB) is a global public health threat
There were 157 multidrug-resistant tuberculosis (MDR-TB) patients and 26 were identified as XDR strains by second-line drug susceptibility testing (DST)
One hundred ninety-five other drug-resistant tuberculosis (DR-TB) and 711 drug-susceptible TB (DS-TB) cases were included in this investigation (Fig. 1)
Summary
The World Health Organization (WHO) has estimated 10.4 million new TB cases in 2016, including 0.49 million multidrug-resistant tuberculosis (MDR-TB) cases[1]. The countries with the largest number of MDR include China, India, and the Russian Federation[1]. China is 1 of the 27 high MDR-TB burden countries. The prevalence of MDR-TB in China was 5.3% in recent years[2]. Concentrated efforts to control TB has resulted in a sharp decrease in the incidence of TB in recent years, China still had the largest number of MDR cases worldwide in 20161. To determine the prevalence and pattern of mutations, drug target genes for rifampin (RIF) and isoniazid (INH) in these MDR-TB strains and other drug-resistant tuberculosis (DR-TB) strains have been sequenced and detected. Interspersed repetitive unit-variable number of tandem repeats (MIRU-VNTR) genotyping were performed to allow a better understanding of MDR-TB genetic lineage and mutant patterns
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