ItemArticle

Rv1899c, an HDAC1ZBTB25-Interacting Protein of Mycobacterium tuberculosis, Promotes Stress Resistance and Immune Evasion in Infected Macrophages

Title
Rv1899c, an HDAC1ZBTB25-Interacting Protein of Mycobacterium tuberculosis, Promotes Stress Resistance and Immune Evasion in Infected Macrophages
Creator
Menon, Arjun M.; Gopichand, Boinapalli; Thomas, Shwetha Susan; Abhinand, Kuniyil; Nair, Bipin G.; Kumar, Geetha B.; Babu, Pradeesh; Arun, K.B.; Edison, Lekshmi K.; Madhavan, Aravind
Description
Rv1899c, a previously identified HDAC1ZBTB25-interacting protein of Mycobacterium tuberculosis, plays a crucial role in bacterial adaptation and immune modulation. Recombinant M. smegmatis-expressing Rv1899c (MS_ Rv1899c) showed enhanced survival under acidic and oxidative stress compared to vector controls, along with improved early intracellular growth in THP1-derived macrophages. This was accompanied by reduced reactive oxygen species (ROS), diminished cytokines associated with inflammation and downregulation of autophagy proteins ATG5, Beclin, and LC3, which ultimately skewed the immune response, suppressing the pro-inflammatory M1 macrophage population. Targeting Rv1899c with 3-aminobenzamide (3-AB) impaired intracellular bacterial survival and restored IL-12B expression, while its combination with the HDAC inhibitor C1994 significantly enhanced bacterial clearance. Structural modelling confirmed the high stereochemical quality of the Rv1899c macrodomain, and computational studies identified 3-AB as the strongest ligand (?5.75 kcal/mol), stabilized through hydrogen bonding and hydrophobic interactions with key residues. Molecular dynamics simulations conducted for 200 ns demonstrated stable proteinligand interactions with consistent parameters, while MM/GBSA analysis indicated favourable binding energy (?G_bind = ?6.6 kcal/mol), largely influenced by van der Waals and electrostatic forces. Together, these findings highlight Rv1899c as a mediator of stress resistance and immune evasion and propose it as a potential therapeutic target against M. tuberculosis. 2025 by the authors.
Source
International Journal of Molecular Sciences;Volume;26;Issue;22;Article No.;10872;
Date
01-01-2025
Publisher
Multidisciplinary Digital Publishing Institute (MDPI)
Subject
autophagy; epigenetics; immune evasion; macrophage polarization; tuberculosis
Coverage
Menon A.M., School of Biotechnology, Amrita Vishwa Vidyapeetham, AmritapuriKerala, Kollam, 690525, India; Gopichand B., School of Biotechnology, Amrita Vishwa Vidyapeetham, AmritapuriKerala, Kollam, 690525, India; Thomas S.S., School of Biotechnology, Amrita Vishwa Vidyapeetham, AmritapuriKerala, Kollam, 690525, India; Abhinand K., School of Biotechnology, Amrita Vishwa Vidyapeetham, AmritapuriKerala, Kollam, 690525, India; Nair B.G., School of Biotechnology, Amrita Vishwa Vidyapeetham, AmritapuriKerala, Kollam, 690525, India; Kumar G.B., School of Biotechnology, Amrita Vishwa Vidyapeetham, AmritapuriKerala, Kollam, 690525, India; Babu P., School of Biotechnology, Amrita Vishwa Vidyapeetham, AmritapuriKerala, Kollam, 690525, India; Arun K.B., Department of Life Sciences, CHRIST (Deemed to be University), Karnataka, Bangalore, 560029, India; Edison L.K., Department of Comparative, Diagnostic, and Population Medicine, College of Veterinary Medicine, University of Florida, Gainesville, 32608, FL, United States; Madhavan A., School of Biotechnology, Amrita Vishwa Vidyapeetham, AmritapuriKerala, Kollam, 690525, India
Rights
All Open Access; Gold Open Access
Relation
ISSN: 16616596;
Format
online
Language
English
Type
Article

Citation

Menon, Arjun M.; Gopichand, Boinapalli; Thomas, Shwetha Susan; Abhinand, Kuniyil; Nair, Bipin G.; Kumar, Geetha B.; Babu, Pradeesh; Arun, K.B.; Edison, Lekshmi K.; Madhavan, Aravind, “Rv1899c, an HDAC1ZBTB25-Interacting Protein of Mycobacterium tuberculosis, Promotes Stress Resistance and Immune Evasion in Infected Macrophages,” CHRIST (Deemed To Be University) Institutional Repository, accessed June 18, 2026, https://archives.christuniversity.in/items/show/23530.

Output Formats