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Antibacterial efficacy of mycobacteriophages against virulent Mycobacterium tuberculosis

Jeyasankar, S and Kalapala, YC and Sharma, PR and Agarwal, R (2024) Antibacterial efficacy of mycobacteriophages against virulent Mycobacterium tuberculosis. In: BMC Microbiology, 24 (1).

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Official URL: https://doi.org/10.1186/s12866-024-03474-3

Abstract

Tuberculosis (TB) remains a major global health concern, with drug-resistant strains posing a significant challenge to effective treatment. Bacteriophage (phage) therapy has emerged as a potential alternative to combat antibiotic resistance. In this study, we investigated the efficacy of widely used mycobacteriophages (D29, TM4, DS6A) against Mycobacterium tuberculosis (M. tuberculosis) under pathophysiological conditions associated with TB, such as low pH and hypoxia. We found that even at low multiplicity of infection (MOI), mycobacteriophages effectively infected M. tuberculosis, got rapidly amplified, and lysed M. tuberculosis, demonstrating their potential as therapeutic agents. Furthermore, we observed a novel phage tolerance mechanism with bacteria forming aggregates after several days of phage treatment. These aggregates were enriched with biofilm components and metabolically active bacteria. However, no phage tolerance was observed upon treatment with the three-phage mixture, highlighting the dynamic interplay between phages and bacteria and emphasizing the importance of phage cocktails. We also observed that phages were effective in lysing bacteria even under low pH and low oxygen concentrations as well as antibiotic-resistant bacteria. Our results provide key insights into phage infection of slow-growing bacteria and suggest that mycobacteriophages can effectively eliminate M. tuberculosis in complex pathophysiological environments like hypoxia and acidic pH. These results can aid in developing targeted phage-based therapies to combat antibiotic-resistant mycobacterial infections. © The Author(s) 2024.

Item Type: Journal Article
Publication: BMC Microbiology
Publisher: BioMed Central Ltd
Additional Information: The copyright for this article belongs to the author.
Keywords: biofilm; drug effect; growth, development and aging; human; microbiology; mycobacteriophage; Mycobacterium tuberculosis; pathogenicity; pH; phage therapy; physiology; therapy; tuberculosis; virology, Biofilms; Humans; Hydrogen-Ion Concentration; Mycobacteriophages; Mycobacterium tuberculosis; Phage Therapy; Tuberculosis
Department/Centre: Division of Interdisciplinary Sciences > Centre for Biosystems Science and Engineering
Date Deposited: 19 Sep 2024 08:49
Last Modified: 19 Sep 2024 08:49
URI: http://eprints.iisc.ac.in/id/eprint/86241

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