Whole-genome sequencing of <i>Mycobacterium tuberculosis</i> for prediction of drug resistance

Yang, Jinghui; Chen, Liang; Wang, Weibing; Yu, Fangyou; Xiong, Hongkai

doi:10.1017/s095026882100279x

Cited by 21 publications

(24 citation statements)

References 40 publications

(44 reference statements)

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“…Although these methods are rapid and straightforward, Mtb continuously evolves through the genomic acquisition of single nucleotide polymorphisms (SNPs), insertions, and deletions (indels), impacting the ability to discriminate strains without the classic regions used for resistance detection [20]. Wholegenome sequencing (WGS), as a molecular diagnostic tool, has been greatly developed in TB research and is clinically useful for predicting drug resistance, lineage, tracing transmission, and defining outbreaks [21][22][23][24][25][26].…”

Section: Introductionmentioning

confidence: 99%

Comparative genomics of drug-resistant strains of Mycobacterium tuberculosis in Ecuador

et al. 2022

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Background Tuberculosis is a serious infectious disease affecting millions of people. In spite of efforts to reduce the disease, increasing antibiotic resistance has contributed to persist in the top 10 causes of death worldwide. In fact, the increased cases of multi (MDR) and extreme drug resistance (XDR) worldwide remains the main challenge for tuberculosis control. Whole genome sequencing is a powerful tool for predicting drug resistance-related variants, studying lineages, tracking transmission, and defining outbreaks. This study presents the identification and characterization of resistant clinical isolates of Mycobacterium tuberculosis including a phylogenetic and molecular resistance profile study by sequencing the complete genome of 24 strains from different provinces of Ecuador. Results Genomic sequencing was used to identify the variants causing resistance. A total of 15/21 isolates were identified as MDR, 4/21 as pre-XDR and 2/21 as XDR, with three isolates discarded due to low quality; the main sub-lineage was LAM (61.9%) and Haarlem (19%) but clades X, T and S were identified. Of the six pre-XDR and XDR strains, it is noteworthy that five come from females; four come from the LAM sub-lineage and two correspond to the X-class sub-lineage. A core genome of 3,750 genes, distributed in 295 subsystems, was determined. Among these, 64 proteins related to virulence and implicated in the pathogenicity of M. tuberculosis and 66 possible pharmacological targets stand out. Most variants result in nonsynonymous amino acid changes and the most frequent genotypes were identified as conferring resistance to rifampicin, isoniazid, ethambutol, para-aminosalicylic acid and streptomycin. However, an increase in the resistance to fluoroquinolones was detected. Conclusion This work shows for the first time the variability of circulating resistant strains between men and women in Ecuador, highlighting the usefulness of genomic sequencing for the identification of emerging resistance. In this regard, we found an increase in fluoroquinolone resistance. Further sampling effort is needed to determine the total variability and associations with the metadata obtained to generate better health policies.

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Section: Introductionmentioning

confidence: 99%

Comparative genomics of drug-resistant strains of Mycobacterium tuberculosis in Ecuador

et al. 2022

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“…In addition, interesting large deletions related to the pncA and gid genes were detected.In turn, non-resistance-conferring mutations were detected in the katG (R463L) and gyrA (E21Q, S95T, G668D) genes that may be useful for the evolutionary characterization of the M. tuberculosis genome. (8,53).…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…Inside all diagnostic innovations in TB for resistance detection, it has been shown that WGS as a molecular diagnostic tool can be used to detect/rule out resistance to all drugs simultaneously (6)(7)(8). It also allows lineage identification, transmission tracing and outbreak definition (7)(8)(9)(10)(11) and is a faster and more effective method than traditional phenotypic DST (12). The use of WGS as a diagnostic tool goes hand in hand with the development and availability of a wide range of bioinformatics tools that facilitate processing and obtaining results quickly and efficiently.…”

Section: Introductionmentioning

confidence: 99%

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A precision overview of genomic resistance screening in isolates ofMycobacterium tuberculosisusing web-based bioinformatics tools

Morey-León

Mejía-Ponce

Pardo

et al. 2023

Preprint

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Tuberculosis (TB) is among the most deadly diseases that affect worldwide, its impact is mainly due to the continuous emergence of resistant isolates during treatment due to the laborious process of resistance diagnosis, non-adherence to treatment and circulation of previously resistant isolates ofMycobacterium tuberculosis. The aim in this study was evaluate the performance and functionalities of web-based tools: Mykrobe, TB-profiler, PhyReSse, KvarQ, and SAM-TB for detecting resistance in isolate ofMycobacterium tuberculosisin comparison with conventional drug susceptibility tests. We used 88M. tuberculosisisolates which were drug susceptibility tested and subsequently fully sequenced and web-based tools analysed. Statistical analysis was performed to determine the correlation between genomic and phenotypic analysis. Our data show that the main sub-lineage was LAM (44.3%) followed by X-type (23.0%) within isolates evaluated. Mykrobe has a higher correlation with DST (98% of agreement and 0.941Cohen's Kappa) for global resistance detection, but SAM-TB, PhyReSse and Mykrobe had a better correlation with DST for first-line drug analysis individually. We have identified that 50% of mutations characterised by all web-based tools were canonical inrpoB, katG,embB, pncA, gyrAandrrsregions. Our findings suggest that SAM-TB, PhyReSse and Mykrobe were the web-based tools more efficient to determine canonical resistance-related mutations, however more analysis should be performed to improve second-line detection. The improvement of surveillance programs for the TB isolates applying WGS tools against first line drugs, MDR-TB and XDR-TB are priorities to discern the molecular epidemiology of this disease in the country.

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“…Our study showed that Beijing strain was positively correlated with this phenotype, isoniazid resistance, reported to be mainly related to the katG gene mutations[ 59 ]. This is similar to the findings of studies in a whole-genome sequencing based study in China[ 60 ], of which 1024 MDR strains were identified from 2019 strains of Mycobacterium tuberculosis .…”

Section: Discussionmentioning

confidence: 99%

Association between Mycobacterium tuberculosis genotype and diabetes mellitus/hypertension: a molecular study

et al. 2022

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Background A paucity of studies focused on the genetic association that tuberculosis (TB) patients with non-communicable diseases (NCDs) are more likely to be infected with Mycobacterium tuberculosis (MTB) with more potent virulence on anti-TB drug resistance than those without NCDs. The study aimed to document the predominant genotype, determine the association between MTB genotypes and NCD status and drug resistance. Methods We conducted a molecular study in 105 TB patients based on a cross-sectional study focused on the comorbid relationship between chronic conditions and TB among 1773 subjects from September 1, 2019 to August 30, 2020 in Guizhou, China. The participants were investigated through face-to-face interviews, followed by NCDs screening. The DNA of MTB isolates was extracted prior to genotyping using 24 loci MIRU-VNTR. The subsequent evaluations were performed by phylogenetic trees, combined with tests of statistical power, Chi-square or Fisher and multivariate logistic regression analysis. Results The Beijing family of Lineage 2 (East Asia) was the predominant genotype accounting for 43.8% (46/105), followed by Lineage 4 (Euro-America) strains, including Uganda I (34.3%, 36/105), and the NEW-1 (9.5%, 10/105). The proportion of Beijing strain in patients with and without NCDS was 28.6% (8/28) and 49.4% (38/77), respectively, with a statistical power test value of 24.3%. No significant association was detected between MTB genotype and NCD status. A low clustering rate (2.9%) was identified, consisting of two clusters. The rates of global, mono-, poly- and multi-drug resistance were 16.2% (17/105), 14.3% (15/105), 1.0% (1/105) and 4.8% (5/105), respectively. The drug-resistant rates of rifampicin, isoniazid, and streptomycin, were 6.7% (7/105), 11.4% (12/105) and 5.7% (6/105), respectively. Isoniazid resistance was significantly associated with the Beijing genotype of Lineage 2 (19.6% versus 5.1%). Conclusions The Lineage 2 East Asia/Beijing genotype is the dominant genotype of the local MTB with endogenous infection preponderating. Not enough evidence is detected to support the association between the MTB genotype and diabetes/hypertension. Isoniazid resistance is associated with the Lineage 2 East Asia/Beijing strain.

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Whole-genome sequencing of Mycobacterium tuberculosis for prediction of drug resistance

Cited by 21 publications

References 40 publications

Comparative genomics of drug-resistant strains of Mycobacterium tuberculosis in Ecuador

Comparative genomics of drug-resistant strains of Mycobacterium tuberculosis in Ecuador

A precision overview of genomic resistance screening in isolates ofMycobacterium tuberculosisusing web-based bioinformatics tools

Association between Mycobacterium tuberculosis genotype and diabetes mellitus/hypertension: a molecular study

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