Host cell transcriptomic response to the multidrug-resistant Mycobacterium tuberculosis clonal outbreak Beijing strain reveals its pathogenic features
Issued Date
2022-01-01
Resource Type
ISSN
21505594
eISSN
21505608
Scopus ID
2-s2.0-85139887894
Pubmed ID
36242542
Journal Title
Virulence
Volume
13
Issue
1
Start Page
1810
End Page
1826
Rights Holder(s)
SCOPUS
Bibliographic Citation
Virulence Vol.13 No.1 (2022) , 1810-1826
Suggested Citation
Prombutara P., Adriansyah Putra Siregar T., Laopanupong T., Kanjanasirirat P., Khumpanied T., Borwornpinyo S., Rai A., Chaiprasert A., Palittapongarnpim P., Ponpuak M. Host cell transcriptomic response to the multidrug-resistant Mycobacterium tuberculosis clonal outbreak Beijing strain reveals its pathogenic features. Virulence Vol.13 No.1 (2022) , 1810-1826. 1826. doi:10.1080/21505594.2022.2135268 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/85043
Title
Host cell transcriptomic response to the multidrug-resistant Mycobacterium tuberculosis clonal outbreak Beijing strain reveals its pathogenic features
Other Contributor(s)
Abstract
The upsurge of multidrug-resistant infections has rendered tuberculosis the principal cause of death among infectious diseases. A clonal outbreak multidrug-resistant triggering strain of Mycobacterium tuberculosis was identified in Kanchanaburi Province, labelled “MKR superspreader,” which was found to subsequently spread to other regions, as revealed by prior epidemiological reports in Thailand. Herein, we showed that the MKR displayed a higher growth rate upon infection into host macrophages in comparison with the H37Rv reference strain. To further elucidate MKR’s biology, we utilized RNA-Seq and differential gene expression analyses to identify host factors involved in the intracellular viability of the MKR. A set of host genes function in the cellular response to lipid pathway was found to be uniquely up-regulated in host macrophages infected with the MKR, but not those infected with H37Rv. Within this set of genes, the IL-36 cytokines which regulate host cell cholesterol metabolism and resistance against mycobacteria attracted our interest, as our previous study revealed that the MKR elevated genes associated with cholesterol breakdown during its growth inside host macrophages. Indeed, when comparing macrophages infected with the MKR to H37Rv-infected cells, our RNA-Seq data showed that the expression ratio of IL-36RN, the negative regulator of the IL-36 pathway, to that of IL-36G was greater in macrophages infected with the MKR. Furthermore, the MKR’s intracellular survival and increased intracellular cholesterol level in the MKR-infected macrophages were diminished with decreased IL-36RN expression. Overall, our results indicated that IL-36RN could serve as a new target against this emerging multidrug-resistant M. tuberculosis strain.