2004Journal of Shanghai MedicaRequires access

Relativity of rpoB Gene Mutations in Mycobacterium Tuberculosis,Multi-drug Resistance and Degree of Resistance to Rifampin

Zhongyi Hu

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Abstract

Purpose To study the relativity of rpoB gene mutations in Mycobacterium tuberculosis multi-drug resistance and degree of resistance to rifampin. Methods The susceptibilities of 58 isolates of M. tuberculosis to four first-line anti-tuberculosis drugs,including isonazid (INH),rifampin (RFP),streptomycin (SM) and ethambutol (EMB),were detected by absolute concentration method and the resistance patterns were analyzed.Then fragments covering 69-bp rifampin resistance determining region were analyzed by DNA sequencing in order to investigate the relationship between the degree of resistance to rifampin and mutational sites as well as genotypes of rpoB gene. Results There were 36 RFP-resistant isolates and 22 RFP-susceptible isolates among the 58 M. tuberculosis strains.All of the 36 rifampin-resistant isolates had mutation in the 69 bp region of rpoB gene,32 isolates (32/36,88.9%) were at least resistant to RFP and INH.Eighteen isolates (18/20,90%) with high level resistance to RFP were related with mutations of codes 531 and 526 in rpoB gene.Two isolates with mutations of two bases in codes 531 and 526 respectively were both mulit-drug rsistantstrains. Conclusions Detection of the mutations of rpoB in M. tuberculosis is helpful to identify the multi-drug resistant isolates since most of RFP-resistant M. tuberculosis strains caused by rpoB gene mutants were resistant to INH.And the degree of resistance to RFP is related with the mutations of rpoB gene.

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Purpose To study the relativity of rpoB gene mutations in Mycobacterium tuberculosis multi-drug resistance and degree of resistance to rifampin. Methods The susceptibilities of 58 isolates of M. tuberculosis to four first-line anti-tuberculosis drugs,including isonazid (INH),rifampin (RFP),streptomycin (SM) and ethambutol (EMB),were detected by absolute concentration method and the resistance patterns were analyzed.Then fragments covering 69-bp rifampin resistance determining region were analyzed by DNA sequencing in order to investigate the relationship between the degree of resistance to rifampin and mutational sites as well as genotypes of rpoB gene. Results There were 36 RFP-resistant isolates and 22 RFP-susceptible isolates among the 58 M. tuberculosis strains.All of the 36 rifampin-resistant isolates had mutation in the 69 bp region of rpoB gene,32 isolates (32/36,88.9%) were at least resistant to RFP and INH.Eighteen isolates (18/20,90%) with high level resistance to RFP were related with mutations of codes 531 and 526 in rpoB gene.Two isolates with mutations of two bases in codes 531 and 526 respectively were both mulit-drug rsistantstrains. Conclusions Detection of the mutations of rpoB in M. tuberculosis is helpful to identify the multi-drug resistant isolates since most of RFP-resistant M. tuberculosis strains caused by rpoB gene mutants were resistant to INH.And the degree of resistance to RFP is related with the mutations of rpoB gene.

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Available abstract

Purpose To study the relativity of rpoB gene mutations in Mycobacterium tuberculosis multi-drug resistance and degree of resistance to rifampin. Methods The susceptibilities of 58 isolates of M. tuberculosis to four first-line anti-tuberculosis drugs,including isonazid (INH),rifampin (RFP),streptomycin (SM) and ethambutol (EMB),were detected by absolute concentration method and the resistance patterns were analyzed.Then fragments covering 69-bp rifampin resistance determining region were analyzed by DNA sequencing in order to investigate the relationship between the degree of resistance to rifampin and mutational sites as well as genotypes of rpoB gene. Results There were 36 RFP-resistant isolates and 22 RFP-susceptible isolates among the 58 M. tuberculosis strains.All of the 36 rifampin-resistant isolates had mutation in the 69 bp region of rpoB gene,32 isolates (32/36,88.9%) were at least resistant to RFP and INH.Eighteen isolates (18/20,90%) with high level resistance to RFP were related with mutations of codes 531 and 526 in rpoB gene.Two isolates with mutations of two bases in codes 531 and 526 respectively were both mulit-drug rsistantstrains. Conclusions Detection of the mutations of rpoB in M. tuberculosis is helpful to identify the multi-drug resistant isolates since most of RFP-resistant M. tuberculosis strains caused by rpoB gene mutants were resistant to INH.And the degree of resistance to RFP is related with the mutations of rpoB gene.

Key concepts: rpoB, Mycobacterium tuberculosis, Ethambutol, Drug resistance, Biology, Tuberculosis, Gene mutation, Rifampicin

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