Early phase of effective treatment induces distinct transcriptional changes in Mycobacterium tuberculosis expelled by pulmonary tuberculosis patients

Abstract Effective treatment reduces a tuberculosis patient's ability to infect others even before they test negative in sputum or culture. Currently, the basis of reduced infectiousness of the Mycobacterium tuberculosis (Mtb) with effective treatment is unclear. We evaluated changes in aerosol...

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Autores principales: Ambreen Shaikh, Kalpana Sriraman, Smriti Vaswani, Vikas Oswal, Sudha Rao, Nerges Mistry
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Lenguaje:EN
Publicado: Nature Portfolio 2021
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Acceso en línea:https://doaj.org/article/beab20d1eaca48a0b78c4747b319a14a
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spelling oai:doaj.org-article:beab20d1eaca48a0b78c4747b319a14a2021-12-02T17:41:18ZEarly phase of effective treatment induces distinct transcriptional changes in Mycobacterium tuberculosis expelled by pulmonary tuberculosis patients10.1038/s41598-021-96902-72045-2322https://doaj.org/article/beab20d1eaca48a0b78c4747b319a14a2021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-96902-7https://doaj.org/toc/2045-2322Abstract Effective treatment reduces a tuberculosis patient's ability to infect others even before they test negative in sputum or culture. Currently, the basis of reduced infectiousness of the Mycobacterium tuberculosis (Mtb) with effective treatment is unclear. We evaluated changes in aerosolized bacteria expelled by patients through a transcriptomic approach before and after treatment initiation (up to 14 days) by RNA sequencing. A distinct change in the overall transcriptional profile was seen post-treatment initiation compared to pretreatment, only when patients received effective treatment. This also led to the downregulation of genes associated with cellular activities, cell wall assembly, virulence factors indicating loss of pathogenicity, and a diminished ability to infect and survive in new host cells. Based on this, we identified genes whose expression levels changed with effective treatment. The observations of the study open up avenues for further evaluating the changes in bacterial gene expression during the early phase of treatment as biomarkers for monitoring response to tuberculosis treatment regimens and provide means of identifying better correlates of Mtb transmission.Ambreen ShaikhKalpana SriramanSmriti VaswaniVikas OswalSudha RaoNerges MistryNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Ambreen Shaikh
Kalpana Sriraman
Smriti Vaswani
Vikas Oswal
Sudha Rao
Nerges Mistry
Early phase of effective treatment induces distinct transcriptional changes in Mycobacterium tuberculosis expelled by pulmonary tuberculosis patients
description Abstract Effective treatment reduces a tuberculosis patient's ability to infect others even before they test negative in sputum or culture. Currently, the basis of reduced infectiousness of the Mycobacterium tuberculosis (Mtb) with effective treatment is unclear. We evaluated changes in aerosolized bacteria expelled by patients through a transcriptomic approach before and after treatment initiation (up to 14 days) by RNA sequencing. A distinct change in the overall transcriptional profile was seen post-treatment initiation compared to pretreatment, only when patients received effective treatment. This also led to the downregulation of genes associated with cellular activities, cell wall assembly, virulence factors indicating loss of pathogenicity, and a diminished ability to infect and survive in new host cells. Based on this, we identified genes whose expression levels changed with effective treatment. The observations of the study open up avenues for further evaluating the changes in bacterial gene expression during the early phase of treatment as biomarkers for monitoring response to tuberculosis treatment regimens and provide means of identifying better correlates of Mtb transmission.
format article
author Ambreen Shaikh
Kalpana Sriraman
Smriti Vaswani
Vikas Oswal
Sudha Rao
Nerges Mistry
author_facet Ambreen Shaikh
Kalpana Sriraman
Smriti Vaswani
Vikas Oswal
Sudha Rao
Nerges Mistry
author_sort Ambreen Shaikh
title Early phase of effective treatment induces distinct transcriptional changes in Mycobacterium tuberculosis expelled by pulmonary tuberculosis patients
title_short Early phase of effective treatment induces distinct transcriptional changes in Mycobacterium tuberculosis expelled by pulmonary tuberculosis patients
title_full Early phase of effective treatment induces distinct transcriptional changes in Mycobacterium tuberculosis expelled by pulmonary tuberculosis patients
title_fullStr Early phase of effective treatment induces distinct transcriptional changes in Mycobacterium tuberculosis expelled by pulmonary tuberculosis patients
title_full_unstemmed Early phase of effective treatment induces distinct transcriptional changes in Mycobacterium tuberculosis expelled by pulmonary tuberculosis patients
title_sort early phase of effective treatment induces distinct transcriptional changes in mycobacterium tuberculosis expelled by pulmonary tuberculosis patients
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/beab20d1eaca48a0b78c4747b319a14a
work_keys_str_mv AT ambreenshaikh earlyphaseofeffectivetreatmentinducesdistincttranscriptionalchangesinmycobacteriumtuberculosisexpelledbypulmonarytuberculosispatients
AT kalpanasriraman earlyphaseofeffectivetreatmentinducesdistincttranscriptionalchangesinmycobacteriumtuberculosisexpelledbypulmonarytuberculosispatients
AT smritivaswani earlyphaseofeffectivetreatmentinducesdistincttranscriptionalchangesinmycobacteriumtuberculosisexpelledbypulmonarytuberculosispatients
AT vikasoswal earlyphaseofeffectivetreatmentinducesdistincttranscriptionalchangesinmycobacteriumtuberculosisexpelledbypulmonarytuberculosispatients
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