Publication: 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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Issued Date
2021-12-01
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ISSN
20452322
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2-s2.0-85100518253
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Mahidol University
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SCOPUS
Bibliographic Citation
Scientific Reports. Vol.11, No.1 (2021)
Suggested Citation
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. Scientific Reports. Vol.11, No.1 (2021). doi:10.1038/s41598-021-82905-x Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/79270
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Title
Transcriptional response to the host cell environment of a multidrug-resistant Mycobacterium tuberculosis clonal outbreak Beijing strain reveals its pathogenic features
Author(s)
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
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
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.