High Frequency of Mutations in the
            <i>rpoB</i>
            Gene in Rifampin-Resistant Clinical Isolates of
            <i>Mycobacterium tuberculosis</i>
            from Singapore

Lee, Ann S. G.; Lim, Irene H. K.; Tang, Lynn L. H.; Wong, Serre-Yu

doi:10.1128/jcm.43.4.2026-2027.2005

Cited by 44 publications

(39 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The DNA sequences of the rpoB whole gene demonstrated that all of the 362 rifamycin-resistant isolates had missense mutations in the rpoB entire gene, while 30 susceptible isolates and 1 reference strain (strain H37Rv) of M. tuberculosis had no mutations in the rpoB whole gene, which was in line with the previous findings that the susceptibility to rifampin and that to rifabutin in M. tuberculosis are closely correlated with mutation of the rpoB gene (9,12,18). Furthermore, more than 95% of RIF r isolates in our study possessed mutations inside the RRDR of the rpoB gene, which was consistent with the data reported by previous researchers (10,17,11). However, there were still 33 kinds of novel mutations outside the RRDR in RIF r /Rfb r isolates, including in 6 (1.9%) isolates with single mutations (2 isolates with V176F, 1 with P206 T R, 2 with Y314 T C, 1 with H323 T Y) in the beginning of the rpoB gene, and also 4 kinds of novel mutations outside the RRDR in RIF r /Rfb s isolates.…”

Section: Discussionsupporting

confidence: 93%

The Beginning of therpoBGene in Addition to the Rifampin Resistance Determination Region Might Be Needed for Identifying Rifampin/Rifabutin Cross-Resistance in Multidrug-Resistant Mycobacterium tuberculosis Isolates from Southern China

Tan

Zhao³

et al. 2012

J Clin Microbiol

View full text Add to dashboard Cite

We aimed to study the distribution and contribution of mutations in the rpoB whole gene in rifampin-resistant/rifabutinresistant (RIF r /Rfb r ) (or RIF/Rfb cross-resistant) clinical Mycobacterium tuberculosis isolates. One standard M. tuberculosis strain (H37Rv) and 392 other clinical M. tuberculosis isolates mainly from Guangdong Province of China whose susceptibilities to rifampin (RIF), rifabutin (Rfb), streptomycin (SM), ethambutol (EMB), and isoniazid (INH) were previously determined were subjected to DNA sequencing of their rpoB whole genes. H37Rv and the 30 drug-susceptible clinical isolates had no mutations in rpoB whole genes. In 43 rifampin-resistant/rifabutin-susceptible (RIF r /Rfb s ) isolates, the most frequent mutation codons were 516 (62.80%), 526 (14.0%), and 533 (6.98%), but codon 531 had no mutation. Twenty-one of the 43 isolates (48.84%) had single mutations of H526L, H526S, D516V, D516Y, and D516F. In 319 RIF r /Rfb r isolates, the most frequent mutation codons were 531 (73.7%) and 526 (18.8%); the mutation frequency for codon 516 was 2.5%, and that for codon 533 was only 0.31%. A total of 82.8% ( A ccording to the data reported by the World Health Organization (WHO) in 2010, an estimated 440,000 cases of multidrug-resistant tuberculosis (MDR-TB) (primary and acquired) arose in 2008. Among all incident TB cases globally, 3.6% are estimated to have MDR-TB (19), so a series of new drugs or alternatives for treatment of MDR-TB has been recommended by WHO since 2008 (20). Rifabutin (Rfb) has been one of the most efficacious drugs and the first-line oral agent recommended by WHO for MDR-TB, but Rfb sometimes has cross-resistance to rifampin (RIF) (2, 4, 15), which implies that the characterization of rpoB mutations in Rfb-resistant (Rfb r ) isolates is not completely the same as that of rpoB mutations in RIF-resistant (RIF r ) isolates. There have been few data supporting this conjecture to this day because of a lack of characterization of rpoB mutations in Rfb r clinical Mycobacterium tuberculosis isolates, so it is very hard to identify the Rfb r isolates from RIF r isolates, even though so many molecular assays for prediction of rifampin susceptibility have been established (8,1,13,3,5). Furthermore, phenotypic drug susceptibility testing is too time-consuming, which is a tremendous obstacle for MDR-TB therapy with rifabutin.According to the results of research presented previously, the mechanism of resistance to rifampin and rifabutin is commonly amino acid exchange in the ␤ subunit (rpoB) of the DNA-directed RNA polymerase. So, the rpoB mutations in M. tuberculosis isolates, whose susceptibility to rifampin, rifabutin, and isoniazid had been previously determined, were characterized after their rpoB whole genes were sequenced.

show abstract

Section: Discussionsupporting

confidence: 93%

The Beginning of therpoBGene in Addition to the Rifampin Resistance Determination Region Might Be Needed for Identifying Rifampin/Rifabutin Cross-Resistance in Multidrug-Resistant Mycobacterium tuberculosis Isolates from Southern China

Tan

Zhao³

et al. 2012

J Clin Microbiol

View full text Add to dashboard Cite

show abstract

“…This finding distinctly reflects the conclusions of one of our recent nationwide study and other reports which showed high rate of mutation in codon 531 as the main cause of RIF resistance in Saudi Arabia. 24,31 On the other hand, INH resistance was dominated with mutations to katG gene codon 315 and mutation in the position 15 of the inhA promoter region, which is in concordance with our previous reports and other international studies. 24,32,33 Fluoroquinolone resistance was 12% among the studied MDR-TB isolates with the mutation majorly in gyrA gene on codons 90 and 94.…”

Section: Discussionsupporting

confidence: 92%

First Insight Into the Fluoroquinolone and Aminoglycoside Resistance of Multidrug-Resistant Mycobacterium tuberculosis in Saudi Arabia

Varghese

Al‐Hajoj

2017

The American Society of Tropical Medicine and Hygiene

View full text Add to dashboard Cite

Abstract. In Saudi Arabia, there were no nationwide screening studies conducted so far to determine the aminoglycoside and fluoroquinolone resistance among multidrug-resistant tuberculosis (MDR-TB) isolates. Therefore, as the first attempt in the country, a retrospective analysis has been conducted on a nationwide collection of 2,956 M. tuberculosis clinical isolates screened with phenotypic drug susceptibility testing to define MDR-TB. Enrolled MDR-TB isolates were subjected to second-line drug susceptibility testing, detection of mutations conferring resistance to aminoglycosides and fluoroquinolone, followed by 24-loci mycobacterial interspersed repetitive unitvariable number of tandem repeat typing and spoligotyping. Overall, 83 isolates were identified as MDR-TB, and 13 (15.7%) isolates showed resistance to second-line drugs. Moxifloxacin (low level) showed higher resistant rates (10.8%) followed by ofloxacin (7.2%), capreomycin (3.6%), kanamycin (3.6%), and amikacin (2.4%). Overall fluoroquinolone resistance was 12%, whereas aminoglycoside resistance was 7.2%. Predominant mutations conferring resistance to fluoroquinolone were found in gyrA A90V and D94G, whereas aminoglycoside resistance was observed only with rrs gene A1401G mutation. The corresponding strain lineages predominated with Indo-Oceanic and EastAfrican Indian origin. Interestingly, none of the isolates with second-line drug resistance was defined as extensively drug-resistant TB (XDR-TB). Surprisingly, many isolates (50.6%) were panresistant to first-line drugs. Saudi Arabia faces considerable burden of fluoroquinolone-and aminoglycoside-resistant MDR-TB. Higher incidence of panresistant MDR-TB reveals a threat for the emergence of XDR-TB strains in the near future.

show abstract

“…Exploring the molecular genetic basis of drug resistance will contribute to the establishment of efficient methods for the rapid identification of drug-resistant M. tuberculosis strains. However, the frequency, location, and type of resistance-associated mutations vary in different geographical areas (1,30,43,52,54).…”

mentioning

confidence: 99%

Molecular Characterization of Multidrug- and Extensively Drug-Resistant Mycobacterium tuberculosis Strains in Jiangxi, China

et al. 2012

View full text Add to dashboard Cite

In this study, a total of 77 multidrug-resistant and extensively drug-resistant (MDR and XDR, respectively) isolates of Mycobacterium tuberculosis were characterized among samples from patients living in Jiangxi province, China. The following two approaches were used: (i) genotyping all drug-resistant isolates by the 15-locus MIRU-VNTR (mycobacterial interspersed repetitive-unit-variable-number tandem-repeat) method and identifying the Beijing family genotype using the RD105 deletion targeted multiplex PCR and (ii) determining the mutation profiles associated with the resistance to the first-line antituberculous drugs rifampin (RIF) and isoniazid (INH) and the second-line drugs ofloxacin (OFX), kanamycin (KAN), amikacin (AMK), and capreomycin (CAP) with DNA sequencing. Six loci were examined: rpoB (for resistance to RIF), katG and mabA-inhA (INH), gyrA and gyrB (OFX), and rrs (KAN, AMK, and CAP). It is shown that the Beijing genotype was predominant (80.5%) among these strains and that the selected drug-resistant strains were genetically diverse, suggesting that they probably had independently acquired drug resistance. In comparison to the phenotypic data, the sensitivities for the detection of RIF, INH, OFX, and KAN/AMK/CAP resistance by DNA sequencing were 94.8, 80.5, 84.6, and 78.9%, respectively. The most prevalent mutations involved in RIF, INH, OFX, and KAN/AMK/CAP resistance were Ser531Leu in rpoB (44.2%), Ser315Thr in katG (55.8%) and C-15T in mabA-inhA (11.7%), Asp94Gly in gyrA (48.7%), and A1401G in rrs (73.7%), respectively. Five novel katG mutants (Trp191Stop, Thr271Pro, Trp328Phe, Leu546Pro, and Asp695Gly) and six new alleles (Ile569Val, Ile572Met, Phe584Ser, Val615Met, Asp626Glu, and Lys972Thr) in the rpoB gene were identified.

show abstract

High Frequency of Mutations in the rpoB Gene in Rifampin-Resistant Clinical Isolates of Mycobacterium tuberculosis from Singapore

Cited by 44 publications

References 10 publications

The Beginning of therpoBGene in Addition to the Rifampin Resistance Determination Region Might Be Needed for Identifying Rifampin/Rifabutin Cross-Resistance in Multidrug-Resistant Mycobacterium tuberculosis Isolates from Southern China

The Beginning of therpoBGene in Addition to the Rifampin Resistance Determination Region Might Be Needed for Identifying Rifampin/Rifabutin Cross-Resistance in Multidrug-Resistant Mycobacterium tuberculosis Isolates from Southern China

First Insight Into the Fluoroquinolone and Aminoglycoside Resistance of Multidrug-Resistant Mycobacterium tuberculosis in Saudi Arabia

Molecular Characterization of Multidrug- and Extensively Drug-Resistant Mycobacterium tuberculosis Strains in Jiangxi, China

Contact Info

Product

Resources

About