Use of whole-genome sequencing to predict Mycobacterium tuberculosis drug resistance in Shanghai, China

Wu, Xiaodong; Gao, Rongliang; Shen, Xin; Guo, Yinjuan; Yang, Jinghui; Wu, Zheyuan; Tan, Guangkun; Wang, Hongxiu; Yu, Fangyou

doi:10.1016/j.ijid.2020.04.039

Cited by 18 publications

(19 citation statements)

References 39 publications

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“…6,42 There was no isolate carried rrs mutation combined with rpsL mutation in this study, suggesting that mutations in rrs and rpsL genes were mutually exclusive. Mutations in rrs and rpsL genes accounted for 68.6% STR resistance, higher than the data from the tertiary care tuberculosis hospital in China 35 and Mexico, 43 but lower than that from other regions, 44,45 indicating that there were regional differences in the mutations associated with STR resistance and additional resistance mechanisms correlated with STR resistance, such as gidB which was reported to contribute 2.4% to 37.5% STR resistance. 42,44,[46][47][48] EMB resistance was mostly associated with mutations within the embB gene (codon 306 as the dominant).…”

Section: Discussionmentioning

confidence: 55%

“…Mutations in rrs and rpsL genes accounted for 68.6% STR resistance, higher than the data from the tertiary care tuberculosis hospital in China 35 and Mexico, 43 but lower than that from other regions, 44,45 indicating that there were regional differences in the mutations associated with STR resistance and additional resistance mechanisms correlated with STR resistance, such as gidB which was reported to contribute 2.4% to 37.5% STR resistance. 42,44,[46][47][48] EMB resistance was mostly associated with mutations within the embB gene (codon 306 as the dominant). 50 In the present study, embB mutations were found in 93.1% EMB resistant isolates, showed a high mutation prevalence compared to previous reports, ranged from 20% to 90.9%.…”

Section: Discussionmentioning

confidence: 55%

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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: Discussionmentioning

confidence: 55%

Section: Discussionmentioning

confidence: 55%

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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“…A mutation in the inhA gene (S94A) was found in one isolate. Sixteen isolates (24.62%) showed simultaneous mutations in the fabG1 gene promoter region (15C>T, 14/65; 8T>C, 2/65) 14 . Fifty-seven ethambutol-resistant isolates harboured mutations in the embB (primarily M306I/ M306L, 27/57; followed by G497A; A435A; T334H; T319C; G406A; S297A; P404S) and embA (including c.-16C>T, c.-12C>T; 5/57) genes 15 , 16 .…”

Section: Resultsmentioning

confidence: 99%

“…The overall sensitivities and specificities for WGS, as mentioned in the results (“ Drug susceptibility testing ” section), demonstrated more than 80% concordance of the results obtained by WGS with pDST in the determination of resistance to isoniazid, rifampicin, pyrazinamide, streptomycin, second-line injectables, and fluoroquinolones, which is consistent with other available studies. studies 14 – 37 . The lower specificity of WGS in ethambutol resistance is due to the genotypic resistance of 23 phenotypically sensitive isolates.…”

Section: Discussionmentioning

confidence: 99%

Whole genome sequencing of multidrug-resistant Mycobacterium tuberculosis isolates collected in the Czech Republic, 2005–2020

Dohál

Dvořáková

Šperková

et al. 2022

Sci Rep

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The emergence and spread of resistant tuberculosis (TB) pose a threat to public health, so it is necessary to diagnose the drug-resistant forms in a clinically short time frame and closely monitor their transmission. In this study, we carried out a first whole genome sequencing (WGS)-based analysis of multidrug resistant (MDR) M. tuberculosis strains to explore the phylogenetic lineages diversity, drug resistance mechanisms, and ongoing transmission chains within the country. In total, 65 isolates phenotypically resistant to at least rifampicin and isoniazid collected in the Czech Republic in 2005–2020 were enrolled for further analysis. The agreement of the results obtained by WGS with phenotypic drug susceptibility testing (pDST) in the determination of resistance to isoniazid, rifampicin, pyrazinamide, streptomycin, second-line injectables and fluoroquinolones was more than 80%. Phylogenetic analysis of WGS data revealed that the majority of MDR M. tuberculosis isolates were the Beijing lineage 2.2.1 (n = 46/65; 70.8%), while the remaining strains belonged to Euro-American lineage. Cluster analysis with a predefined cut-off distance of less than 12 single nucleotide polymorphisms between isolates showed 19 isolates in 6 clusters (clustering rate 29.2%), located mainly in the region of the capital city of Prague. This study highlights the utility of WGS as a high-resolution approach in the diagnosis, characterization of resistance patterns, and molecular-epidemiological analysis of resistant TB in the country.

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“…In recent studies, embB Gly406Ser was found in ethambutol-resistant Mtb strains. 29 , 33 The mutations embB Ala356Val and Ser380Asn are rare, and their functions need to be verified via additional investigation.…”

Section: Discussionmentioning

confidence: 99%

Analysis of Factors Influencing Multidrug-Resistant Tuberculosis and Validation of Whole-Genome Sequencing in Children with Drug-Resistant Tuberculosis

Zhang¹,

Zhao²,

Zhang³

et al. 2021

IDR

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Objective Pediatric tuberculosis (TB) is one of the top ten causes of death in children. Our study was to analyze influencing factors of multidrug-resistant tuberculosis (MDR-TB) and validation of whole-genome sequencing (WGS) used in children with drug-resistant TB (DR-TB). Methods All Mycobacterium tuberculosis (Mtb) strains were isolated from patients aged below 18 years old of Children’s Hospital of Chongqing Medical University, China. A total of 208 Mtb isolates were tested for eight anti-TB drugs with phenotypic drug susceptibility test (DST) and for genetic prediction of the susceptible profile with WGS. The patients corresponding to each strain were grouped according to drug resistance and genotype. Influencing factors of MDR-TB and DR-TB were analyzed. Results According to the phenotypic DST and WGS, 82.2% of Mtb strains were susceptible to all eight drugs, and 6.3% were MDR-TB. Using the phenotypic DSTs as the gold standard, the kappa value of WGS to predict isoniazid, rifampin, ethambutol, rifapentine, prothionamide, levofloxacin, moxifloxacin and amikacin was 0.84, 0.89, 0.59, 0.86, 0.89, 0.82, 0.88 and 1.00, respectively. There was significant difference in the distribution of severe TB, diagnosis, treatment and outcome between MDR and drug-susceptible group (P<0.05). The distribution of severe TB and treatment between DR and drug-susceptible group was statistically different (P<0.05). The results of binary logistic regression showed that Calmette–Guérin bacillus (BCG) vaccine is the protective factor for MDR-TB (OR=0.19), and MDR-TB is the risk factor for PTB and EPTB (OR=17.98). Conclusion The BCG vaccine is a protective factor for MDR-TB, and MDR-TB might not be confined to pulmonary infection, spreading to extrapulmonary organs in children. MDR-TB had more severe cases and a lower recovery rate than drug-susceptible TB. WGS could provide an accurate prediction of drug susceptibility test results for anti-TB drugs, which are needed for the diagnosis and precise treatment of TB in children.

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Use of whole-genome sequencing to predict Mycobacterium tuberculosis drug resistance in Shanghai, China

Cited by 18 publications

References 39 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

Whole genome sequencing of multidrug-resistant Mycobacterium tuberculosis isolates collected in the Czech Republic, 2005–2020

Analysis of Factors Influencing Multidrug-Resistant Tuberculosis and Validation of Whole-Genome Sequencing in Children with Drug-Resistant Tuberculosis

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