Relationship between rifampin MICs for and rpoB mutations of Mycobacterium tuberculosis strains isolated in Japan

Ohno, Hideaki; Koga, Hironobu; Kohno, Shigeru; Tashiro, Takayoshi; Hara, Kohei

doi:10.1128/aac.40.4.1053

Cited by 130 publications

(78 citation statements)

References 25 publications

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“…The combination of mutations involving katG S315T mutation was 95.1% ( n = 442), and this mutation is described as having the association with higher levels of resistance to INH (MIC, ≥100 µg/ml). This data is consistent with earlier reports [21,32–34]. …”

Section: Discussionsupporting

confidence: 94%

Molecular patterns of multidrug resistance of Mycobacterium tuberculosis in Georgia

Shubladze

Tadumadze

Bablishvili

2013

International Journal of Mycobacteriology

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Background Tuberculosis (TB) infections caused by multidrug-resistant Mycobacterium tuberculosis (MDR MTB) remain a significant public health concern worldwide. Georgia has a high prevalence of MDR MTB. The genetic mechanisms underlying the emergence of MDR MTB strains in this region are poorly understood and need to be determined for developing better strategies for TB control. This study investigated the frequency of major drug resistance mutations across rpoB, katG and inhA loci of Georgian MDR MTB strains and explored differences between new and previously treated patients. A total of 634 MTB strains were examined for which an MDR phenotype had been previously determined by the proportions method. The GenoType®MTBDRplus system was applied to screen the strains for the presence of rpoB (S531L, H526D, H526Y, and D516V), katG (S315T) and inhA promoter region (C15T and T8C) mutations. The target loci were amplified by PCR and then hybridized with the respective site-specific and wild type (control) probes. Results Out of the 634 isolates tested considered by phenotypic testing to be resistant to RIF and INH, this resistance was confirmed by the GenoType®MTBDRplus assay in 575 (90.7%) isolates. RIF resistance was seen in 589 (92.9%) and INH resistance was seen in 584 (92.1%); 67.2% and 84.3% of MDR strains harbored respectively rpoB S531L and katG S315T mutations (generally known as having low or no fitness cost in MTB). The inhA C15T mutation was detected in 22.6% of the strains, whereas rpoB H526D, rpoB H526Y, rpoB D516V and inhA T8C were revealed at a markedly lower frequency (≤5.2%). The specific mutations responsible for the RIF resistance of 110 isolates (17.4%) could not be detected as no corresponding mutant probe was indicated in the assay. There was no specific association of the presence of mutations with the gender/age groups. All types of prevailing mutations had higher levels in new cases. A great majority of the Georgian MDR MTB strains have a strong preference for the drug resistance mutations carrying no or low fitness cost. Thus, it can be suggested that MDR MTB strains with such mutations will continue to arise in Georgia at a high frequency even in the absence of antibiotic pressure.

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Section: Discussionsupporting

confidence: 94%

Molecular patterns of multidrug resistance of Mycobacterium tuberculosis in Georgia

Shubladze

Tadumadze

Bablishvili

2013

International Journal of Mycobacteriology

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“…9,13,22,26,36,37 Mutations of codon 531, 526, and 516 have been reported as the most frequent mutations in the mutation hotspot region of the rpoB gene of MTB worldwide. 3,23,36 In the present study, the majority of mutations occurred at codon 526, and the mutation frequency (48.4%) observed was slightly higher than frequencies reported by China (40%), 36 Japan (35%), 16 and Korea (38%). 9 However, the frequency of occurrence of the mutation at codon 526 in India, the closest neighbor to Sri Lanka, is much higher (93%) as reported by Sharma et al (2003).…”

Section: Discussioncontrasting

confidence: 78%

“…24 The frequency of mutation at codon 531 (9.7%) was comparatively low in MTB isolates from Sri Lanka in relation to mutation frequencies reported by other countries, including India (47%), 10 Australia (52%), 37 Vietnam (31%), 4 and Poland (41%). 23 However, the base change observed at codon 531 was a TCG to TTG (transition mutation) as commonly reported by several Asian countries ( Japan, 16 China, 36 Korea, 9 and India 11 ) and other countries such as Greece 12 and Italy. 18 Previous studies have reported that a mutation at codon 531 is frequently associated with the codon 526 mutation in certain regions of the world.…”

Section: Discussionmentioning

confidence: 87%

“…25,27 Most of RIF resistant MTB strains from different countries appear to harbor specific point mutations in the rifampicin resistance-determining region (RRDR) of the rpoB gene, which comprises an 81-bp region containing codons 507-533. 11,12,16,30 In addition, studies have also revealed a significant contribution to RIF resistance through mutations in the region outer to RRDR of the rpoB gene, suggesting that, the nature and frequency of mutations in the rpoB gene of RIF resistant M. tuberculosis clinical isolates vary considerably, between different geographical regions. 10,11,[17][18][19] Further, it has been reported that there is discordance between results of phenotypic methods and genotypic methods that are based on RRDR mutations used for the detection of drug resistant TB.…”

Section: Introductionmentioning

confidence: 97%

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Geographical Profile ofrpoBGene Mutations in Rifampicin ResistantMycobacterium tuberculosisIsolates in Sri Lanka

Adikaram

Perera²,

Wijesundera³

2012

Microbial Drug Resistance

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“…In contrast, a low degree of drug-resistance (MIC ≥ 12.5 μg/ml) is conferred by nucleotide substitutions in codons 514, 521, 533 [29]. Mutations in codon 516 are also associated with a high degree of resistance (MIC ≥ 64 μg/ml) [30, 31]. Although some studies report similar results, H526L and H526N mutations are the exception; in these cases, the MIC values did not exceed 8 and 16 μg/ml, respectively.…”

Section: Discussionmentioning

confidence: 99%

Characterization of extensively drug-resistant Mycobacterium tuberculosis isolates circulating in Siberia

et al. 2014

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BackgroundThe spread of multidrug-resistant (MDR) and extensively drug-resistant (XDR) Mycobacterium tuberculosis compromises effective control of tuberculosis (TB) in Siberia. Early identification of drug-resistant isolates is, therefore, crucial for effective treatment of this disease. The aim of this study was to conduct drug susceptibility testing and identify mutations in drug resistance genes in clinical isolates of M. tuberculosis from some TB patients presenting for treatment in Siberia.MethodsThirty randomly selected clinical isolates of M. tuberculosis were obtained from the Novosibirsk Research Institute of Tuberculosis, Russia. Isolates were screened for drug resistance and characterized by variable number of tandem repeats (VNTR)-typing using 15 standard and four additional loci. Deligotyping on multiple large sequences was performed using 10 loci.ResultsTwenty-nine of the isolates were assigned XDR status. Twenty-eight isolates belonged to the M. tuberculosis Beijing family, from which 11 isolates were considered the M11 type (39%), two the M2 type (7%), and one the M33 type (3%). Seventeen isolates (60.7%) from this family exhibited unique genetic patterns. The remaining two isolates belonged to the Latino-American Mediterranean family. Gene sequences (rpoB, katG, rrs, rpsL, tlyA, gidB, gyrA, gyrB) were analyzed to identify mutations that confer resistance to rifampicin, isoniazid, amikacin, kanamycin, capreomycin, and ofloxacin. The most common mutations among the XDR isolates were S531L in RpoB, S315T in KatG, various codon 94 mutations in gyrA, A90V in GyrA, K43R in RpsL, and 1401 A → G in rrs; these confer resistance to rifampicin, isoniazid, ofloxacin, streptomycin and kanamycin/capreomycin, respectively. There was high congruence between the two typing methods (VNTR typing and deligotyping) and RD105, RD149, RD152, RD181, and RD207 regions of difference were absent from the 28 Beijing family isolates.ConclusionsDeligotyping can be used for rapid and reliable screening of M. tuberculosis isolates, followed by more in-depth genotyping. Identification of Beijing family isolates with extensive drug resistance confirms that such strains have epidemiological importance in Siberia. Rapid detection of mutations that lead to drug resistance should facilitate selection of effective drug therapies, and the development of early prevention strategies to combat this infection.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2334-14-478) contains supplementary material, which is available to authorized users.

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Relationship between rifampin MICs for and rpoB mutations of Mycobacterium tuberculosis strains isolated in Japan

Cited by 130 publications

References 25 publications

Molecular patterns of multidrug resistance of Mycobacterium tuberculosis in Georgia

Molecular patterns of multidrug resistance of Mycobacterium tuberculosis in Georgia

Geographical Profile ofrpoBGene Mutations in Rifampicin ResistantMycobacterium tuberculosisIsolates in Sri Lanka

Characterization of extensively drug-resistant Mycobacterium tuberculosis isolates circulating in Siberia

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