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

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-ge...

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Autores principales: Muzondiwa, Dillon, Hlanze, Hleliwe, Reva, Oleg N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8300818/
https://www.ncbi.nlm.nih.gov/pubmed/34356778
http://dx.doi.org/10.3390/antibiotics10070857
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author Muzondiwa, Dillon
Hlanze, Hleliwe
Reva, Oleg N.
author_facet Muzondiwa, Dillon
Hlanze, Hleliwe
Reva, Oleg N.
author_sort Muzondiwa, Dillon
collection PubMed
description 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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spelling pubmed-83008182021-07-24 The Epistatic Landscape of Antibiotic Resistance of Different Clades of Mycobacterium tuberculosis Muzondiwa, Dillon Hlanze, Hleliwe Reva, Oleg N. Antibiotics (Basel) Article 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. MDPI 2021-07-15 /pmc/articles/PMC8300818/ /pubmed/34356778 http://dx.doi.org/10.3390/antibiotics10070857 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Muzondiwa, Dillon
Hlanze, Hleliwe
Reva, Oleg N.
The Epistatic Landscape of Antibiotic Resistance of Different Clades of Mycobacterium tuberculosis
title The Epistatic Landscape of Antibiotic Resistance of Different Clades of Mycobacterium tuberculosis
title_full The Epistatic Landscape of Antibiotic Resistance of Different Clades of Mycobacterium tuberculosis
title_fullStr The Epistatic Landscape of Antibiotic Resistance of Different Clades of Mycobacterium tuberculosis
title_full_unstemmed The Epistatic Landscape of Antibiotic Resistance of Different Clades of Mycobacterium tuberculosis
title_short The Epistatic Landscape of Antibiotic Resistance of Different Clades of Mycobacterium tuberculosis
title_sort epistatic landscape of antibiotic resistance of different clades of mycobacterium tuberculosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8300818/
https://www.ncbi.nlm.nih.gov/pubmed/34356778
http://dx.doi.org/10.3390/antibiotics10070857
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