Mutations in rpoB and katG genes of multidrug resistant mycobacterium tuberculosis undetectable using genotyping diagnostic methods

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dc.contributor.authorTakawira, Faustinos Tatenda
dc.contributor.authorMandishora, Racheal S. D.
dc.contributor.authorDhlamini, Zephaniah
dc.contributor.authorMunemo, Ellen
dc.contributor.authorStray-Pedersen, Babill
dc.date.accessioned2017-09-21T13:41:36Z
dc.date.accessioned2023-06-23T14:00:53Z
dc.date.available2017-09-21T13:41:36Z
dc.date.available2023-06-23T14:00:53Z
dc.date.issued2017-06-28
dc.descriptionJournal Articleen_US
dc.description.abstractIntroduction: Tuberculosis remains the leading causes of death worldwide with frequencies of mutations in rifampicin and isoniazid resistant Mycobacterium tuberculosis isolates varying according to geographical location. There is limited information in Zimbabwe on specific antibiotic resistance gene mutation patterns in MTB and hence, increased rate of discordant results and mortality due to inappropriate antibiotic prescriptions. The rpoB and katG genes molecular markers are used for detecting rifampicin and isoniazid resistance respectively. Some mutations within these gene sequences are associated with drug resistance as they directly alter gene function. The objectives of this research was to determine the drug resistance profiles in M. tuberculosis isolates that are phenotypically resistant but not detected by the GeneXpert and MTBDRplus kit and also to detect mutations in the rpoB and katG genes which are not detected by the Hain Genotype MTBDRplus kit and GeneXpert diagnosis. Methods: PCR was used for the amplification of the rpoB and katG genes from MTB isolates collected from human clinical samples between 2008 and 2015. The genes were sequenced and compared to the wild type MTB H37Rv rpoB (accession number L27989) and kat G genes (KP46920), respectively. Sequence analysis results were compared to genotyping results obtained from molecular assays and culture results of all isolates. Results: The most frequent mutation responsible for rifampicin resistance was (25/92) S531L that was detected by using all molecular assays. Some inconsistencies were observed between phenotypic and genotypic assay results for both katG and rpoB genes in 30 strains. For these, eight codons; G507S, T508A, L511V, del513-526, P520P, L524L, R528H, R529Q and S531F were novel mutations. In addition, the I572P/F, E562Q, P564S, and Q490Y mutations were identified as novel mutations outside the rifampicin resistance determining region. In katG gene, amino acid changes to threonine, asparagine and isoleucine exhibited high degrees of polymorphism such as V473N, D311N, and L427I. The R463L (20/92) amino acid substitution was most common but was not associated with isoniazid resistance. Conclusion: These finding indicate that molecular assay kit diagnosis that is based on the rpoB and katG genes should be improved to cater for the genetic variations associated with the geographic specificity of the target genes and be able to detect most prevalent mutations in different areas.en_US
dc.identifier.citationTakawira F.T et el. 2017. Mutations in rpoB and katG genes of multidrug resistant mycobacterium tuberculosis undetectable using genotyping diagnostic methods: Pan African Medical Journal 27.en_US
dc.identifier.issn1937- 8688
dc.identifier.urihttp://196.220.97.103:4000/handle/123456789/800
dc.language.isoenen_US
dc.publisherAfrican Field Epidemiology Networken_US
dc.subjectMutationen_US
dc.subjectRpoBen_US
dc.subjectGeneXperten_US
dc.subjecthainsen_US
dc.subjectgenotypeen_US
dc.subjectMTBDRplusen_US
dc.subjectMycobacteriumen_US
dc.subjecttuberculosisen_US
dc.subjectsequencingen_US
dc.subjectDNAen_US
dc.subjectPCRen_US
dc.subjectKatGen_US
dc.titleMutations in rpoB and katG genes of multidrug resistant mycobacterium tuberculosis undetectable using genotyping diagnostic methodsen_US
dc.typeArticleen_US
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