Molecular analysis of codon 548 in the rpoB gene involved in Mycobacterium tuberculosis resistance to rifampin

Yu Tze Horng, Wen Yih Jeng, Yih Yuan Chen, Che Hung Liu, Horng Yunn Dou, Jen Jyh Lee, Kai Chih Chang, Chih Ching Chien, Po Chi Soo

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Most Mycobacterium tuberculosis rifampin-resistant strains have been associated with mutations in an 81-bp rifampin resistance- determining region (RRDR) in the gene rpoB. However, if this region alone were targeted, rifampin-resistant strains with mutations outside the RRDR would not be detected. In this study, among 51 rifampin-resistant clinical isolates analyzed by sequencing 1,681-bp-long DNA fragments containing the RRDR, 47 isolates contained mutations within the RRDR, three isolates contained mutations both within and outside the RRDR, and only one isolate had a single missense mutation (Arg548His) located outside the RRDR. A drug susceptibility test of recombinant Mycobacterium smegmatis and M. tuberculosis isolates carrying mutated rpoB (Arg548His) showed an increased MIC for rifampin compared to that of the control strains. Modeling of the Arg548His mutant RpoB-DNA complex revealed that the His548 side chain formed a more stable hydrogen bond structure than did Arg548, reducing the flexibility of the rifampin-resistant cluster II region of RpoB, suggesting that the RpoB Arg548His mutant does not effectively interact with rifampin and results in bacterial resistance to the drug. This is the first report on the relationship between the mutation in codon 548 of RpoB and rifampin resistance in tuberculosis. The novel mutational profile of the rpoB gene described here will contribute to the comprehensive understanding of rifampin resistance patterns and to the development of a useful tool for simple and rapid drug susceptibility tests.

Original languageEnglish
Pages (from-to)1542-1548
Number of pages7
JournalAntimicrobial agents and chemotherapy
Volume59
Issue number3
DOIs
Publication statusPublished - 2015 Mar 1

Fingerprint

Rifampin
Mycobacterium tuberculosis
Codon
Genes
Mutation
Bacterial Drug Resistance
Mycobacterium smegmatis
DNA
Missense Mutation
Pharmaceutical Preparations
Hydrogen
Tuberculosis

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Cite this

Horng, Yu Tze ; Jeng, Wen Yih ; Chen, Yih Yuan ; Liu, Che Hung ; Dou, Horng Yunn ; Lee, Jen Jyh ; Chang, Kai Chih ; Chien, Chih Ching ; Soo, Po Chi. / Molecular analysis of codon 548 in the rpoB gene involved in Mycobacterium tuberculosis resistance to rifampin. In: Antimicrobial agents and chemotherapy. 2015 ; Vol. 59, No. 3. pp. 1542-1548.
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Molecular analysis of codon 548 in the rpoB gene involved in Mycobacterium tuberculosis resistance to rifampin. / Horng, Yu Tze; Jeng, Wen Yih; Chen, Yih Yuan; Liu, Che Hung; Dou, Horng Yunn; Lee, Jen Jyh; Chang, Kai Chih; Chien, Chih Ching; Soo, Po Chi.

In: Antimicrobial agents and chemotherapy, Vol. 59, No. 3, 01.03.2015, p. 1542-1548.

Research output: Contribution to journalArticle

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AU - Horng, Yu Tze

AU - Jeng, Wen Yih

AU - Chen, Yih Yuan

AU - Liu, Che Hung

AU - Dou, Horng Yunn

AU - Lee, Jen Jyh

AU - Chang, Kai Chih

AU - Chien, Chih Ching

AU - Soo, Po Chi

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