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A host blood transcriptional signature differentiates multi-drug/rifampin-resistant tuberculosis (MDR/RR-TB) from drug susceptible tuberculosis: a pilot study

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Abstract

Background

Tuberculosis (TB), caused by the bacterium Mycobacterium tuberculosis is one of the top thirteen causes of death worldwide. The major challenge to control TB is the emergence of drug-resistant tuberculosis (DR-TB); specifically, multi-drug resistant TB which are resistant to the most potent drugs; rifampin and isoniazid. Owing to the inconsistencies of the current diagnostic methods, a single test cannot identify the whole spectrum of DR-TB associated mutations. Recently, host blood transcriptomics has gained attention as a promising technique that develops disease-specific RNA signatures/biomarkers. However, studies on host transcriptomics infected with DR-TB is limited. Herein, we intended to identify genes/pathways that are differentially expressed in multi-drug/rifampin resistant TB (MDR/RR-TB) in contrast to drug susceptible TB.

Method and results

We conducted blood RNA sequencing of 10 pulmonary TB patients (4; drug susceptible and 6; DR-TB) and 55 genes that were differentially expressed in MDR/RR-TB from drug-susceptible/mono-resistant TB were identified. CD300LD, MYL9, VAMP5, CARD17, CLEC2B, GBP6, BATF2, ETV7, IFI27 and FCGR1CP were found to be upregulated in MDR/RR-TB in all comparisons, among which CLEC2B and CD300LD were not previously linked to TB. In comparison pathway analysis, interferon alpha/gamma response was upregulated while Wnt/beta catenin signaling, lysosome, microtubule nucleation and notch signaling were downregulated.

Conclusion

Up/down-regulation of immunity related genes/pathways speculate the collective effect of hosts’ attempt to fight against continuously multiplying DR-TB bacteria and the bacterial factors to fight against the host defense. The identified genes/pathways could act as MDR/RR-TB biomarkers, hence, further research on their clinical use should be encouraged.

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Acknowledgements

The authors would like to thank the staff of General Teaching Hospital, Kandy, Sri Lanka and National Hospital for Respiratory Diseases, Welisara, Sri Lanka, for their unconditional support. We also acknowledge Ms. Anuradha Ekanayake and Ms. Chameena Weerarathne’s generous support.

Funding

This work was supported by the National Science Foundation, Sri Lanka (NSF/PSF/ICRP/2017/HS/01). The corresponding author Dhammika Magana-Arachchi was the grant recipient.

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Authors and Affiliations

  1. Molecular Microbiology & Human Diseases Project, National Institute of Fundamental Studies, Hantana Road, Kandy, 20000, Sri Lanka

    Pavithra Madamarandawala & Dhammika Magana-Arachchi

  2. Department of Molecular Biology and Biotechnology, Faculty of Science, University of Peradeniya, Peradeniya, 20400, Sri Lanka

    Sanath Rajapakse

  3. National Hospital for Respiratory Diseases, Welisara, 11010, Sri Lanka

    Bandu Gunasena

  4. Respiratory Diseases Treatment Unit, General Teaching Hospital, Kandy, 20000, Sri Lanka

    Dushantha Madegedara

Authors
  1. Pavithra Madamarandawala
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  2. Sanath Rajapakse
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  3. Bandu Gunasena
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  4. Dushantha Madegedara
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  5. Dhammika Magana-Arachchi
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Contributions

DM-A contributed to the study conception, and design. Material preparation, sample collection, data collection, analysis, and the preparation of the first draft of the manuscript was performed by PM. The study was supervised by SR, DM, BG and DM-A. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Dhammika Magana-Arachchi.

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Conflict of interest

The authors have no relevant financial or non-financial interests to disclose.

Ethical approval

Ethical approval was obtained from the ethical review committee at the general teaching hospital, Kandy, Sri Lanka. All the patients agreed to the study protocol and provided written informed consent prior to recruitment. This study was performed in line with the principles of the Declaration of Helsinki.

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Madamarandawala, P., Rajapakse, S., Gunasena, B. et al. A host blood transcriptional signature differentiates multi-drug/rifampin-resistant tuberculosis (MDR/RR-TB) from drug susceptible tuberculosis: a pilot study. Mol Biol Rep 50, 3935–3943 (2023). https://doi.org/10.1007/s11033-023-08307-6

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  • DOI: https://doi.org/10.1007/s11033-023-08307-6

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