Analysis of whiB7 in Mycobacterium tuberculosis reveals novel AT-hook deletion mutations

Abstract Mutations in whiB7 have been associated with both hypersusceptibility and resistance to various antibiotics in Mycobacterium tuberculosis (Mtb). Unlocking the secrets of antibiotic resistance in the bacterium, we examined mutations in the coding sequences of whiB7 of over 40,000 diverse Mtb...

Full description

Bibliographic Details
Main Authors: Olabisi Flora Davies-Bolorunduro, Bharkbhoom Jaemsai, Wuthiwat Ruangchai, Worakorn Phumiphanjarphak, Pakorn Aiewsakun, Prasit Palittapongarnpim
Format: Article
Language:English
Published: Nature Portfolio 2023-08-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-023-40152-2
_version_ 1797453292232507392
author Olabisi Flora Davies-Bolorunduro
Bharkbhoom Jaemsai
Wuthiwat Ruangchai
Worakorn Phumiphanjarphak
Pakorn Aiewsakun
Prasit Palittapongarnpim
author_facet Olabisi Flora Davies-Bolorunduro
Bharkbhoom Jaemsai
Wuthiwat Ruangchai
Worakorn Phumiphanjarphak
Pakorn Aiewsakun
Prasit Palittapongarnpim
author_sort Olabisi Flora Davies-Bolorunduro
collection DOAJ
description Abstract Mutations in whiB7 have been associated with both hypersusceptibility and resistance to various antibiotics in Mycobacterium tuberculosis (Mtb). Unlocking the secrets of antibiotic resistance in the bacterium, we examined mutations in the coding sequences of whiB7 of over 40,000 diverse Mtb isolates. Our results unveil the dominant c.191delG (Gly64delG) mutation, present in all members of the lineage L1.2.2 and its impact on WhiB7's conserved GVWGG-motif, causing conformational changes and deletion of the C-terminal AT-hook. Excitingly, we discovered six unique mutations associated with partial or total deletion of the AT-hook, specific to certain sublineages. Our findings suggest the selective pressures driving these mutations, underlining the potential of genomics to advance our understanding of Mtb's antibiotic resistance. As tuberculosis remains a global health threat, our study offers valuable insights into the diverse nature and functional consequences of whiB7 mutations, paving the way for the development of novel therapeutic interventions.
first_indexed 2024-03-09T15:20:43Z
format Article
id doaj.art-9f63c5ce20d74ca1adefa8ae1bc94bd6
institution Directory Open Access Journal
issn 2045-2322
language English
last_indexed 2024-03-09T15:20:43Z
publishDate 2023-08-01
publisher Nature Portfolio
record_format Article
series Scientific Reports
spelling doaj.art-9f63c5ce20d74ca1adefa8ae1bc94bd62023-11-26T12:49:46ZengNature PortfolioScientific Reports2045-23222023-08-011311910.1038/s41598-023-40152-2Analysis of whiB7 in Mycobacterium tuberculosis reveals novel AT-hook deletion mutationsOlabisi Flora Davies-Bolorunduro0Bharkbhoom Jaemsai1Wuthiwat Ruangchai2Worakorn Phumiphanjarphak3Pakorn Aiewsakun4Prasit Palittapongarnpim5Pornchai Matangkasombut Center for Microbial Genomics, Department of Microbiology, Faculty of Science, Mahidol UniversityDepartment of Microbiology, Faculty of Science, Mahidol UniversityPornchai Matangkasombut Center for Microbial Genomics, Department of Microbiology, Faculty of Science, Mahidol UniversityDepartment of Microbiology, Faculty of Science, Mahidol UniversityPornchai Matangkasombut Center for Microbial Genomics, Department of Microbiology, Faculty of Science, Mahidol UniversityPornchai Matangkasombut Center for Microbial Genomics, Department of Microbiology, Faculty of Science, Mahidol UniversityAbstract Mutations in whiB7 have been associated with both hypersusceptibility and resistance to various antibiotics in Mycobacterium tuberculosis (Mtb). Unlocking the secrets of antibiotic resistance in the bacterium, we examined mutations in the coding sequences of whiB7 of over 40,000 diverse Mtb isolates. Our results unveil the dominant c.191delG (Gly64delG) mutation, present in all members of the lineage L1.2.2 and its impact on WhiB7's conserved GVWGG-motif, causing conformational changes and deletion of the C-terminal AT-hook. Excitingly, we discovered six unique mutations associated with partial or total deletion of the AT-hook, specific to certain sublineages. Our findings suggest the selective pressures driving these mutations, underlining the potential of genomics to advance our understanding of Mtb's antibiotic resistance. As tuberculosis remains a global health threat, our study offers valuable insights into the diverse nature and functional consequences of whiB7 mutations, paving the way for the development of novel therapeutic interventions.https://doi.org/10.1038/s41598-023-40152-2
spellingShingle Olabisi Flora Davies-Bolorunduro
Bharkbhoom Jaemsai
Wuthiwat Ruangchai
Worakorn Phumiphanjarphak
Pakorn Aiewsakun
Prasit Palittapongarnpim
Analysis of whiB7 in Mycobacterium tuberculosis reveals novel AT-hook deletion mutations
Scientific Reports
title Analysis of whiB7 in Mycobacterium tuberculosis reveals novel AT-hook deletion mutations
title_full Analysis of whiB7 in Mycobacterium tuberculosis reveals novel AT-hook deletion mutations
title_fullStr Analysis of whiB7 in Mycobacterium tuberculosis reveals novel AT-hook deletion mutations
title_full_unstemmed Analysis of whiB7 in Mycobacterium tuberculosis reveals novel AT-hook deletion mutations
title_short Analysis of whiB7 in Mycobacterium tuberculosis reveals novel AT-hook deletion mutations
title_sort analysis of whib7 in mycobacterium tuberculosis reveals novel at hook deletion mutations
url https://doi.org/10.1038/s41598-023-40152-2
work_keys_str_mv AT olabisifloradaviesbolorunduro analysisofwhib7inmycobacteriumtuberculosisrevealsnovelathookdeletionmutations
AT bharkbhoomjaemsai analysisofwhib7inmycobacteriumtuberculosisrevealsnovelathookdeletionmutations
AT wuthiwatruangchai analysisofwhib7inmycobacteriumtuberculosisrevealsnovelathookdeletionmutations
AT worakornphumiphanjarphak analysisofwhib7inmycobacteriumtuberculosisrevealsnovelathookdeletionmutations
AT pakornaiewsakun analysisofwhib7inmycobacteriumtuberculosisrevealsnovelathookdeletionmutations
AT prasitpalittapongarnpim analysisofwhib7inmycobacteriumtuberculosisrevealsnovelathookdeletionmutations