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ORIGINAL RESEARCH article

Front. Microbiol.
Sec. Microbial Symbioses
Volume 15 - 2024 | doi: 10.3389/fmicb.2024.1344857

Expression of a unique M. tuberculosis DNA MTase Rv1509 in M. smegmatis alters the gene expression pattern and enhances virulence

Provisionally accepted
Manjunath P Manjunath P 1Javeed Ahmad Javeed Ahmad 2Dr Jasmine Samal Dr Jasmine Samal 3Anshu Rani Anshu Rani 4Javaid A. Sheikh Javaid A. Sheikh 5Sheeba Zarin Sheeba Zarin 6Yashika Ahuja Yashika Ahuja 6ANWAR ALAM ANWAR ALAM 7Seyed E. Hasnain Seyed E. Hasnain 8*Nasreen Z. Ehtesham Nasreen Z. Ehtesham 6
  • 1 Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States
  • 2 National Institute of Allergy and Infectious Diseases (NIH), Bethesda, Maryland, United States
  • 3 National Institute of Pathology (ICMR), New Delhi, Delhi, India
  • 4 National Institutes of Health (NIH), Bethesda, Maryland, United States
  • 5 Department of Biotechnology, Jamia Hamdard University, New Delhi, NCT of Delhi, India
  • 6 Sharda University, Greater Noida, Uttar Pradesh, India
  • 7 Department of Biotechnology, Sharda University, Greater Noida, Uttar Pradesh, India
  • 8 Indian Institute of Technology Delhi, New Delhi, National Capital Territory of Delhi, India

The final, formatted version of the article will be published soon.

    Mycobacterium tuberculosis (M. tb) genome encompasses 4173 genes, about a quarter of which remain uncharacterized and hypothetical. Considering the current limitations associated with the diagnosis and treatment of tuberculosis, it is imperative to comprehend the disease pathomechanism, and host-pathogen interactions and for identifying new drug targets for intervention strategies. Using in-silico comparative genome analysis, we identified one of the M. tb genes Rv1509 as a signature protein exclusively present in M. tb. To explore the role of Rv1509, a likely methyl transferase, we constructed a knock-in Mycobacterium smegmatis (M. smegmatis) constitutively expressing Rv1509 (Ms_Rv1509). The Ms_Rv1509 led to differential expression of many transcriptional regulator genes as assessed by RNA-seq analysis. Further, in-vitro and invivo studies demonstrated an enhanced survival of Ms_Rv1509 inside the host macrophages.Ms_Rv1509 also promoted phagolysosomal escape inside macrophages, to boost bacterial replication and dissemination. In-vivo infection studies revealed that Ms_Rv1509 survives better than BCG and causes pathological manifestations in the pancreas after intraperitoneal infection.Long-time survival of Ms_Rv1509 resulted in lymphocyte migration, increased T regulatory cells, giant cell formation, and likely granuloma formation in the pancreas, pointing towards the role of Rv1509 in M. tb pathogenesis.

    Keywords: BCG, Macrophage Activation, phagolysosomal escape, RNA-Seq, 'Signature sequence', Transcription regulator, T-regulatory cells

    Received: 30 Nov 2023; Accepted: 15 Apr 2024.

    Copyright: © 2024 P, Ahmad, Samal, Rani, Sheikh, Zarin, Ahuja, ALAM, Hasnain and Ehtesham. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Seyed E. Hasnain, Indian Institute of Technology Delhi, New Delhi, 110016, National Capital Territory of Delhi, India

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