1887

Abstract

Resistance to rifampin (RIF) in infection is associated with mutations in the gene coding for the β-subunit of RNA polymerase. The contribution of various mutations to the development and level of RIF resistance remains elusive.

Various mutations may be associated with differential levels of RIF resistance.

This study aimed to investigate the relationship between specific mutations and the MICs of RIF and rifabutin (RFB) against .

Of the 195 clinical isolates, 105 and 90 isolates were randomly selected from isolates resistant to RIF and sensitive to RIF, respectively. The MICs of 12 agents for isolates were determined using commercial Sensititre MIC plates and the broth microdilution method. Strains were screened for mutations by DNA extraction, gene amplification and DNA sequence analysis.

One hundred isolates (95.24 %) were found to have mutations in the RIF-resistance-determining region (RRDR) of the gene. Three mutations were identified in 90 RIF-susceptible isolates. Out of 105 isolates, 86 (81.90 %) were cross-resistant to both RIF and RFB. The most frequent mutation occurred at codons 450 and 445. We also found a novel nine-nucleotide (ATCATGCAT) deletion (between positions 1543 and 1551) in the gene in two strains (1.90 %) with resistance to RIF, but susceptibility to RFB. In addition, the mutation frequency at codon 450 was significantly higher in RIF-resistant/RFB-resistant (RIF/RFB) strains than in RIF/RFB strains (75.58 % versus 21.05 %, <0.01), whereas the mutation frequency at codon 435 was significantly lower in RIF/RFB strains than in RIF/RFB strains (1.16 % versus 26.32 %, <0.01).

Our data support previous findings, which reported that various mutations are associated with differential levels of RIF resistance. The specific mutations in the gene in RIF/RFB isolates differed from those in the RIF/RFB isolates. A novel deletion mutation in the RRDR might be associated with resistance to RIF, but not to RFB. Further clinical studies are required to investigate the efficacy of RFB in the treatment of infections caused by strains harbouring these mutations.

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2021-01-28
2021-02-26
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