Frequency of Codon 306 Mutations in embB Gene of Mycobacterium tuberculosis Resistant to Ethambutol: A Systematic Review and Meta-Analysis

Mohammadi, Bahman; Ramazanzadeh, Rashid; Nouri, Bijan; Rouhi, Samaneh

doi:10.4103/ijpvm.ijpvm_114_19

Cited by 9 publications

(13 citation statements)

References 54 publications

(47 reference statements)

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“…The phenomenon was also reported in previous studies. 8 , 51 Overall 6.0% of EMB-susceptible isolates also carried mutations in embB , which is close to the data from a previous study (6.5%), 52 which maybe attributed to the narrow range of EMB critical concentrations for differentiating resistant and susceptible strains, and the possible presence of microcolonies that are difficult to detect visually. 53 A previous study shows that, using the EMB concentration with 1.6 µg/mL instead of 2.0 µg/mL in L-J slants by the proportional method, more than 90% EMB-susceptible isolates that carried embB 306 mutations could be successfully recognized as EMB-resistant isolates, while the EMB susceptible isolates with wild-type embB were not changed.…”

Section: Discussionsupporting

confidence: 87%

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Prevalence and Molecular Characteristics Based on Whole Genome Sequencing of Mycobacterium tuberculosis Resistant to Four Anti-Tuberculosis Drugs from Southern Xinjiang, China

Anwaierjiang¹,

Wang²,

Liu³

et al. 2021

IDR

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Drug-resistant tuberculosis is a major public health problem, especially in the southern region of Xinjiang, China; however, there is little information regarding drug resistance profiles and mechanism of Mycobacterium tuberculosis in this area. The aim of this study was to determine the prevalence and molecular characteristics of M. tuberculosis resistant to four anti-tuberculosis drugs from this area. Methods: Three hundred and forty-six isolates from the southern region of Xinjiang, China were included and used to perform phenotypic drug susceptibility testing and whole genome sequencing (WGS). Mutations in seven loci associated with drug resistance, including rpoB for rifampicin (RMP), katG, inhA promoter and oxyR-ahpC for isoniazid (INH), rrs 530 and 912 loops and rpsL for streptomycin (STR), and embB for ethambutol (EMB), were characterized. Results: Among 346 isolates, 106, 60, 70 and 29 were resistant to INH, RMP, STR and EMB, respectively; 132 were resistant to at least one of the four anti-tuberculosis drugs and 51 were multi-drug resistant (MDR). Beijing genotype and retreated patients showed a significantly increased risk for developing MDR tuberculosis. Compared with the phenotypic data, the sensitivity and specificity for WGS to predict resistance were 96.7% and 98.6% for RMP, 75.5% and 97.1% for INH, 68.6% and 99.6% for STR, 93.1% and 93.7% for EMB, respectively. The most common mutations conferring RMP, INH, STR and EMB resistance were Ser450Leu (51.7%) in rpoB, Ser315Thr (44.3%) in katG, Lys43Arg (35.7%) in rpsL and Met306Val (24.1%) in embB. Conclusion:This study provides the first information on the prevalence and molecular characters of drug resistant M. tuberculosis in the southern region of Xinjiang, China, which will be helpful for choosing early detection methods for drug resistance (ig, molecular methods) and subsequently initiation of proper therapy of tuberculosis in this area.

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Section: Discussionsupporting

confidence: 87%

“…Studies on EMB resistance showed that mutations outside embB codon 306 and 406, do occur but are quite rare. 51 , 55 However, substitutions at other codons were identified in 12 EMB-susceptible and eight EMB-resistant isolates. Two novel mutations embB Ala495Thr and Met575Ile were found only in EMB resistant isolates.…”

Section: Discussionmentioning

confidence: 99%

Prevalence and Molecular Characteristics Based on Whole Genome Sequencing of Mycobacterium tuberculosis Resistant to Four Anti-Tuberculosis Drugs from Southern Xinjiang, China

Anwaierjiang¹,

Wang²,

Liu³

et al. 2021

IDR

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“…Drug resistance to EMB is due mainly to effects related to the biosynthesis of arabinogalactan [38,39]. This is caused by mutations of genes related to biological activity, and the mutation in position 306 of the gene embB is considered to be the main cause of drug resistance [40,41]. In concordance with this, our results showed that 25 of the 36 EMB resistant specimens had M306V mutations, while 9 were M306I mutations and 2 were M306L mutations.…”

Section: Discussionsupporting

confidence: 83%

Establishment and evaluation of an overlap extension polymerase chain reaction technique for rapid and efficient detection of drug-resistance in Mycobacterium tuberculosis

Ouyang

Yuan

et al. 2022

Infect Dis Poverty

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Background Rapid and accurate detection of drug resistance in Mycobacterium tuberculosis is critical for effective control of tuberculosis (TB). Herein, we established a novel, low cost strategy having high accuracy and speed for the detection of M. tuberculosis drug resistance, using gene splicing by overlap extension PCR (SOE PCR). Methods The SOE PCR assay and Sanger sequencing are designed and constructed to detect mutations of rpoB, embB, katG, and inhA promoter, which have been considered as the major contributors to rifampicin (RFP), isoniazid (INH), and ethambutol (EMB) resistance in M. tuberculosis. One hundred and eight M. tuberculosis isolates came from mycobacterial cultures of TB cases at Chongqing Public Health Medical Center in China from December 2018 to April 2019, of which 56 isolates were tested with the GeneXpert MTB/RIF assay. Performance evaluation of the SOE PCR technique was compared with traditional mycobacterial culture and drug susceptibility testing (DST) or GeneXpert MTB/RIF among these isolates. Kappa identity test was used to analyze the consistency of the different diagnostic methods. Results We found that the mutations of S531L, S315T and M306V were most prevalent for RFP, INH and EMB resistance, respectively, in the 108 M. tuberculosis isolates. Compared with phenotypic DST, the sensitivity and specificity of the SOE PCR assay for resistance detection were 100.00% and 88.00% for RFP, 94.64% and 94.23% for INH, and 68.97% and 79.75% for EMB, respectively. Compared with the GeneXpert MTB/RIF, the SOE PCR method was completely consistent with results of the GeneXpert MTB/RIF, with a concordance of 100% for resistance to RFP. Conclusions In present study, a novel SOE PCR diagnostic method was successfully developed for the accurate detection of M. tuberculosis drug resistance. Our results using this method have a high consistency with that of traditional phenotypic DST or GeneXpert MTB/RIF, and SOE PCR testing in clinical isolates can also be conducted rapidly and simultaneously for detection of drug resistance to RFP, EMB, and INH. Graphical Abstract

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“…There were some shortcomings in our research. For the main purpose of this study, which was to screen the DR gene mutation patterns of resistant clinical M. tb , the drug-sensitive isolates were not detected, although some MMs were also found in phenotype-sensitive isolates [ 6 , 8 , 11 , 15 , 26 ]. The screening of DR isolates only focused on the reported main genes which were significantly related to resistant M. tb , and some new DR gene analysis was not included.…”

Section: Discussionmentioning

confidence: 99%

“…Of INH-resistant isolates, 42% to 95% have at least one mutation (the most common mutation is in codon 315) in katG , which encodes catalase-peroxidase, and 8% to 20% have mutations in the inhA open reading frame [ 9 ]. Of EMB-resistant isolates, 30% to 67% have at least one mutation in embB, which encodes arabinosyltransferase [ 10 , 11 ]. Of STR-resistant isolates, 56% to 72% have mutations in rpsL , which encodes ribosomal protein S12 [ 12 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

Analysis on Drug-Resistance-Associated Mutations among Multidrug-Resistant Mycobacterium tuberculosis Isolates in China

Jia

Sun

2021

Antibiotics

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As the causative bacteria of tuberculosis, Mycobacteriumtuberculosis (M. tb) is aggravated by the emergence of its multidrug-resistant isolates in China. Mutations of six of the most frequently reported resistant genes (rpoB, katG, inhA, embB, gyrA, and rpsL) were detected for rifampicin (RIF), isoniazid (INH), ethambutol (EMB), ofloxacin (OFX), and streptomycin (STR) in this study. The amino acid missense mutations (MMs) and their corresponding single nucleotide polymorphism mutations for all drug-resistant (DR) isolates are described in detail. All isolates were divided into non-extensively drug-resistant (Non-XDR) and preXDR/XDR groups. No statistical differences were detected among MMs and linked MMs (LMs) between the two groups, except for rpsL 88 (p = 0.037). In the preXDR/XDR group, the occurrence of MMs in rpoB, katG, and inhA developed phenotypic resistance and MMs of rpoB 531, katG 315, rpsL 43, and rpsL 88 could develop high levels of DR. It is necessary to carry out epidemiological investigations of DR gene mutations in the local region, and thus provide necessary data to support the design of new technologies for rapid detection of resistant M. tb and the optimization of detection targets.

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Frequency of Codon 306 Mutations in embB Gene of Mycobacterium tuberculosis Resistant to Ethambutol: A Systematic Review and Meta-Analysis

Cited by 9 publications

References 54 publications

Prevalence and Molecular Characteristics Based on Whole Genome Sequencing of Mycobacterium tuberculosis Resistant to Four Anti-Tuberculosis Drugs from Southern Xinjiang, China

Prevalence and Molecular Characteristics Based on Whole Genome Sequencing of Mycobacterium tuberculosis Resistant to Four Anti-Tuberculosis Drugs from Southern Xinjiang, China

Establishment and evaluation of an overlap extension polymerase chain reaction technique for rapid and efficient detection of drug-resistance in Mycobacterium tuberculosis

Analysis on Drug-Resistance-Associated Mutations among Multidrug-Resistant Mycobacterium tuberculosis Isolates in China

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