Resistance Sniffer: An online tool for prediction of drug resistance patterns of Mycobacterium tuberculosis isolates using next generation sequencing data

Muzondiwa, Dillon; Mutshembele, Awelani; Pierneef, Rian; Reva, Oleg N.

doi:10.1016/j.ijmm.2020.151399

Cited by 22 publications

(19 citation statements)

References 54 publications

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“…TBProfiler v3.0.4 23 was used to analyze all 222 genomes in-silico to infer phylogenetic lineages and drug resistance profiles using small variants and big deletions associated with drug resistance that are present in a robust library of recently updated mutation database which contains new anti-TB drugs such as cycloserine, delamanid, bedaquiline, clofazimine, para-aminosalicylic acid, linezolid and ethionamide [commit b2af444 on 21st December 2020 ( https://github.com/jodyphelan/tbdb )] using freebayes 28 as the variant calling option. In order to validate the results, Mykrobe predictor 29 and Resistance Sniffer 30 was used to analyze the newly sequenced Nigerian samples for comparison.…”

Section: Methodsmentioning

confidence: 99%

Whole genome sequencing of clinical samples reveals extensively drug resistant tuberculosis (XDR TB) strains from the Beijing lineage in Nigeria, West Africa

Olawoye

Uwanibe

Kunle-Ope

et al. 2021

Sci Rep

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Multi-drug (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) continues to be a global public health problem especially in high TB burden countries like Nigeria. Many of these cases are undetected and go on to infect high risk individuals. Clinical samples from positive rifampicin resistant Xpert®MTB/Rif assay were subjected to direct whole genome sequencing and bioinformatics analysis to identify the full antibiotics resistance and lineage profile. We report two (2) XDR TB samples also belonging to the East-Asian/Beijing family of lineage 2 Mycobacterium tuberculosis complex from clinical samples in Nigeria. Our findings further reveal the presence of mutations that confer resistance to first-line drugs (rifampicin, isoniazid, ethambutol and pyrazanimide), second-line injectables (capreomycin, streptomycin, kanamycin and/or amikacin) and at least one of the fluoroquinolones (ofloxacin, moxifloxacin, levofloxacin and/or ciprofloxacin) in both samples. The genomic sequence data from this study not only provide the first evidence of XDR TB in Nigeria and West Africa, but also emphasize the importance of WGS in accurately detecting MDR and XDR TB, to ensure adequate and proper management treatment regimens for affected individuals. This will greatly aid in preventing the spread of drug resistance TB in high burden countries.

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Section: Methodsmentioning

confidence: 99%

Whole genome sequencing of clinical samples reveals extensively drug resistant tuberculosis (XDR TB) strains from the Beijing lineage in Nigeria, West Africa

Olawoye

Uwanibe

Kunle-Ope

et al. 2021

Sci Rep

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“…Studies on epistatic networks relevant to DR and virulence evolution will allow predicting outbreaks of DR infections in advance at the time of formation of an epistatic background of antibiotic resistance. This idea was realized in our recent software tool, Resistance Sniffer, which uses NGS data to predict Mtb isolates, which potentially may develop DR in the course of antibiotic therapy [35].…”

Section: Discussionmentioning

confidence: 99%

“…Understanding the stepwise molecular processes of the accumulation of initial prerequisite mutations acting as a gateway for the emergence of MDR is another gap in our knowledge [34]. Knowing the ways of escaping the fitness cost of DR mutations by MDR-TB will uncover molecular targets for new antibiotics and allow predicting Mtb clinical isolates with a potential to develop MDR in the near future [35].…”

Section: Introductionmentioning

confidence: 99%

The Epistatic Landscape of Antibiotic Resistance of Different Clades of Mycobacterium tuberculosis

2021

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Drug resistance (DR) remains a global challenge in tuberculosis (TB) control. In order to develop molecular-based diagnostic methods to replace the traditional culture-based diagnostics, there is a need for a thorough understanding of the processes that govern TB drug resistance. The use of whole-genome sequencing coupled with statistical and computational methods has shown great potential in unraveling the complexity of the evolution of DR-TB. In this study, we took an innovative approach that sought to determine nonrandom associations between polymorphic sites in Mycobacterium tuberculosis (Mtb) genomes. Attributable risk statistics were applied to identify the epistatic determinants of DR in different clades of Mtb and the possible evolutionary pathways of DR development. It was found that different lineages of Mtb exploited different evolutionary trajectories towards multidrug resistance and compensatory evolution to reduce the DR-associated fitness cost. Epistasis of DR acquisition is a new area of research that will aid in the better understanding of evolutionary biological processes and allow predicting upcoming multidrug-resistant pathogens before a new outbreak strikes humanity.

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“…An important drawback to the general application of these approaches as diagnostic tools is that they just provide predictions. Although genotypic-phenotypic linkage seems to be strong in the case of mutation driven resistance [156] and stand-alone informatic tools have been developed to link genotypic-phenotypic information [157] , in the case of resistance genes the phenotype of resistance depends not only on the ARG, but also on its genomic context [24] . Further, sequence-based approaches cannot identify as yet unknown mechanisms of resistance that may contribute to the phenotype.…”

Section: Whole-genome Based Diagnosis and Epidemiology Of Antibiotic Resistancementioning

confidence: 99%

Antibiotic resistance: Time of synthesis in a post-genomic age

Gil-Gil

Ochoa-Sánchez

Baquero

et al. 2021

Computational and Structural Biotechnology Journal

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Resistance Sniffer: An online tool for prediction of drug resistance patterns of Mycobacterium tuberculosis isolates using next generation sequencing data

Cited by 22 publications

References 54 publications

Whole genome sequencing of clinical samples reveals extensively drug resistant tuberculosis (XDR TB) strains from the Beijing lineage in Nigeria, West Africa

Whole genome sequencing of clinical samples reveals extensively drug resistant tuberculosis (XDR TB) strains from the Beijing lineage in Nigeria, West Africa

The Epistatic Landscape of Antibiotic Resistance of Different Clades of Mycobacterium tuberculosis

Antibiotic resistance: Time of synthesis in a post-genomic age

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