Mycobacterial Interspersed Repetitive Unit Can Predict Drug Resistance of Mycobacterium tuberculosis in China

Abstract

Background: Recently, Mycobacterial Interspersed Repetitive Unit (MIRU) was supposed to be associated with drug resistance in Mycobacterium tuberculosis (M. tuberculosis), but whether the association exists actually in local strains in China was still unknown. This research was conducted to explore that association and the predictability of MIRU to drug resistance of Tuberculosis (TB).Methods: The clinical isolates were collected and the susceptibility test were conducted with Lowenstein–Jensen (LJ) medium for five anti-TB drug. Based on PCR of MIRU-VNTR (Variable Number of Tandem Repeat) genotyping, we tested the number of the repeat unite of MIRU. Then, we used logistic regression to evaluate the association between 15 MIRU and drug resistance. In addition, we explored the most suitable MIRU locus of identified MIRU loci for drug resistance by multivariate logistic regression.Results: Of the 102 strains, one isolate was resistant to rifampicin and one isolate was resistant to streptomycin. Among these fifteen MIRU, there was a association between MIRU loci polymorphism and anti-tuberculosis drug resistance, ETRB (P = 0.03, OR = 0.19, 95% CI 0.05–0.81) and ETRC (P = 0.01, OR = 0.14, 95% CI 0.03–0.64) were negatively related to isoniazid resistance; MIRU20 (P = 0.05, OR = 2.87, 95% CI 1.01–8.12) was positively associated with ethambutol resistance; and QUB11a (P = 0.02, OR = 0.79, 95% CI 0.65–0.96) was a negative association factor of p-aminosalicylic acid resistance.Conclusion: Our research showed that MIRU loci may predict drug resistance of tuberculosis in China. However, the mechanism still needs further exploration.

Clustering and recent transmission of <em>Mycobacterium tuberculosis</em> in a Chinese population

“…30 Although several optimal loci have been suggested for genotyping homogenous Mtb , 16 , 31 , 32 15 loci have been widely used in China. 33 – 35 In the current study, the total HGDI for all 15 loci was 0.999. The locus Qub11b had the highest HGDI (0.762), while the HGDI of ETRC was very low (0.036).…”

Genome analyses of 174 strains of Mycobacterium tuberculosis provide insight into the evolution of drug resistance and reveal potential drug targets

“…The Rv0488 (S) ( dN/dS =0.26) gene that encodes a putative amino acid transporter was observed to have the lowest dN/dS value. The presence of a protective factor for INH resistance, ETRC, 210 bp upstream of Rv0488 has been reported to be negatively linked with INH resistance [ 54 ]. Thus, our analysis suggests Rv0488 is probably the most stabilized among MDT genes and can be considered as a suitable target.…”

The mutation rate of rpoB gene showed an upward trend with the increase of MIRU10, MIRU39 and QUB4156 repetitive number

“…MIRU loci are located in the spacer of DNA coding genes, and their specific functions are not clear. Some scholars [ 23 – 25 ] believed that the difference in the copy number of MIRU sites upstream of the coding gene will lead to the difference in the number of ribosomal binding sites (RBS), thus affecting the transcription and expression level of the gene. The coding product encoded by the fadB gene downstream of MIRU10 is an oxidoreductase that binds to flavin adenine dinucleotide (FAD), the oxidative stress response induced by this gene may be one of the mechanisms of anti-tuberculosis drugs killing bacteria [ 26 ].…”