Transcriptional response to the host cell environment of a multidrug-resistant Mycobacterium tuberculosis clonal outbreak Beijing strain reveals its pathogenic features

Abstract Tuberculosis is a global public health problem with emergence of multidrug-resistant infections. Previous epidemiological studies of tuberculosis in Thailand have identified a clonal outbreak multidrug-resistant strain of Mycobacterium tuberculosis in the Kanchanaburi province, designated “...

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Autores principales:	Pakorn Aiewsakun, Pinidphon Prombutara, Tegar Adriansyah Putra Siregar, Thanida Laopanupong, Phongthon Kanjanasirirat, Tanawadee Khumpanied, Suparerk Borwornpinyo, Pirut Tong-Ngam, Alisa Tubsuwan, Prapaporn Srilohasin, Angkana Chaiprasert, Wuthiwat Ruangchai, Prasit Palittapongarnpim, Therdsak Prammananan, Brian C. VanderVen, Marisa Ponpuak
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/cc4308bcab2248c6a6699842dda13551
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spelling	oai:doaj.org-article:cc4308bcab2248c6a6699842dda135512021-12-02T14:06:19ZTranscriptional response to the host cell environment of a multidrug-resistant Mycobacterium tuberculosis clonal outbreak Beijing strain reveals its pathogenic features10.1038/s41598-021-82905-x2045-2322https://doaj.org/article/cc4308bcab2248c6a6699842dda135512021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-82905-xhttps://doaj.org/toc/2045-2322Abstract Tuberculosis is a global public health problem with emergence of multidrug-resistant infections. Previous epidemiological studies of tuberculosis in Thailand have identified a clonal outbreak multidrug-resistant strain of Mycobacterium tuberculosis in the Kanchanaburi province, designated “MKR superspreader”, and this particular strain later was found to also spread to other regions. In this study, we elucidated its biology through RNA-Seq analyses and identified a set of genes involved in cholesterol degradation to be up-regulated in the MKR during the macrophage cell infection, but not in the H37Rv reference strain. We also found that the bacterium up-regulated genes associated with the ESX-1 secretion system during its intracellular growth phase, while the H37Rv did not. All results were confirmed by qRT-PCR. Moreover, we showed that compounds previously shown to inhibit the mycobacterial ESX-1 secretion system and cholesterol utilisation, and FDA-approved drugs known to interfere with the host cholesterol transportation were able to decrease the intracellular survival of the MKR when compared to the untreated control, while not that of the H37Rv. Altogether, our findings suggested that such pathways are important for the MKR’s intracellular growth, and potentially could be targets for the discovery of new drugs against this emerging multidrug-resistant strain of M. tuberculosis.Pakorn AiewsakunPinidphon PrombutaraTegar Adriansyah Putra SiregarThanida LaopanupongPhongthon KanjanasiriratTanawadee KhumpaniedSuparerk BorwornpinyoPirut Tong-NgamAlisa TubsuwanPrapaporn SrilohasinAngkana ChaiprasertWuthiwat RuangchaiPrasit PalittapongarnpimTherdsak PrammanananBrian C. VanderVenMarisa PonpuakNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Pakorn Aiewsakun Pinidphon Prombutara Tegar Adriansyah Putra Siregar Thanida Laopanupong Phongthon Kanjanasirirat Tanawadee Khumpanied Suparerk Borwornpinyo Pirut Tong-Ngam Alisa Tubsuwan Prapaporn Srilohasin Angkana Chaiprasert Wuthiwat Ruangchai Prasit Palittapongarnpim Therdsak Prammananan Brian C. VanderVen Marisa Ponpuak Transcriptional response to the host cell environment of a multidrug-resistant Mycobacterium tuberculosis clonal outbreak Beijing strain reveals its pathogenic features
description	Abstract Tuberculosis is a global public health problem with emergence of multidrug-resistant infections. Previous epidemiological studies of tuberculosis in Thailand have identified a clonal outbreak multidrug-resistant strain of Mycobacterium tuberculosis in the Kanchanaburi province, designated “MKR superspreader”, and this particular strain later was found to also spread to other regions. In this study, we elucidated its biology through RNA-Seq analyses and identified a set of genes involved in cholesterol degradation to be up-regulated in the MKR during the macrophage cell infection, but not in the H37Rv reference strain. We also found that the bacterium up-regulated genes associated with the ESX-1 secretion system during its intracellular growth phase, while the H37Rv did not. All results were confirmed by qRT-PCR. Moreover, we showed that compounds previously shown to inhibit the mycobacterial ESX-1 secretion system and cholesterol utilisation, and FDA-approved drugs known to interfere with the host cholesterol transportation were able to decrease the intracellular survival of the MKR when compared to the untreated control, while not that of the H37Rv. Altogether, our findings suggested that such pathways are important for the MKR’s intracellular growth, and potentially could be targets for the discovery of new drugs against this emerging multidrug-resistant strain of M. tuberculosis.
format	article
author	Pakorn Aiewsakun Pinidphon Prombutara Tegar Adriansyah Putra Siregar Thanida Laopanupong Phongthon Kanjanasirirat Tanawadee Khumpanied Suparerk Borwornpinyo Pirut Tong-Ngam Alisa Tubsuwan Prapaporn Srilohasin Angkana Chaiprasert Wuthiwat Ruangchai Prasit Palittapongarnpim Therdsak Prammananan Brian C. VanderVen Marisa Ponpuak
author_facet	Pakorn Aiewsakun Pinidphon Prombutara Tegar Adriansyah Putra Siregar Thanida Laopanupong Phongthon Kanjanasirirat Tanawadee Khumpanied Suparerk Borwornpinyo Pirut Tong-Ngam Alisa Tubsuwan Prapaporn Srilohasin Angkana Chaiprasert Wuthiwat Ruangchai Prasit Palittapongarnpim Therdsak Prammananan Brian C. VanderVen Marisa Ponpuak
author_sort	Pakorn Aiewsakun
title	Transcriptional response to the host cell environment of a multidrug-resistant Mycobacterium tuberculosis clonal outbreak Beijing strain reveals its pathogenic features
title_short	Transcriptional response to the host cell environment of a multidrug-resistant Mycobacterium tuberculosis clonal outbreak Beijing strain reveals its pathogenic features
title_full	Transcriptional response to the host cell environment of a multidrug-resistant Mycobacterium tuberculosis clonal outbreak Beijing strain reveals its pathogenic features
title_fullStr	Transcriptional response to the host cell environment of a multidrug-resistant Mycobacterium tuberculosis clonal outbreak Beijing strain reveals its pathogenic features
title_full_unstemmed	Transcriptional response to the host cell environment of a multidrug-resistant Mycobacterium tuberculosis clonal outbreak Beijing strain reveals its pathogenic features
title_sort	transcriptional response to the host cell environment of a multidrug-resistant mycobacterium tuberculosis clonal outbreak beijing strain reveals its pathogenic features
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/cc4308bcab2248c6a6699842dda13551
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Transcriptional response to the host cell environment of a multidrug-resistant Mycobacterium tuberculosis clonal outbreak Beijing strain reveals its pathogenic features

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