Journal Article

Antimycobacterial activity of 2-methyl-adenosine

Esther W. Barrow, Louise Westbrook, Namita Bansal, William J. Suling, Joseph A. Maddry, William B. Parker and William W. Barrow

in Journal of Antimicrobial Chemotherapy

Published on behalf of British Society for Antimicrobial Chemotherapy

Volume 52, issue 5, pages 801-808
Published in print November 2003 | ISSN: 0305-7453
Published online November 2003 | e-ISSN: 1460-2091 | DOI: http://dx.doi.org/10.1093/jac/dkg444
Antimycobacterial activity of 2-methyl-adenosine

Show Summary Details

Preview

Objectives: The aims of this study were to assess the in vitro activity of 2-methyl-adenosine against Mycobacterium tuberculosis and evaluate, and to intracellular efficacy, and to evaluate its effectiveness against M. tuberculosis in a persistent state model and examine its potential mechanism of action.

Methods: In vitro activity was determined by means of a colorimetric microdilution broth assay. Intracellular activity was assessed with a Mono Mac 6 human monocytic cell line. A hypoxic shift-down model was used to evaluate the effect of 2-methyl-adenosine on M. tuberculosis in a persistent state. Mechanism-of-action studies were conducted by examining the effect of 2-methyl-adenosine on the uptake of appropriate radiolabelled precursors into respective mycobacterial macromolecular components.

Results: Studies confirmed the in vitro activity of 2-methyl-adenosine against M. tuberculosis and demonstrated intracellular efficacy against M. tuberculosis within macrophages. 2-Methyl-adenosine was able to significantly affect the viability of M. tuberculosis in a hypoxic shift-down model previously described to simulate the persistent state that results during tuberculosis. Mechanism-of-action studies revealed that the immediate inhibitory effects of 2-methyl-adenosine were associated with protein and DNA synthesis and not RNA synthesis.

Conclusions: Results indicate that 2-methyl-adenosine, or similar derivatives, might be effective against M. tuberculosis infections during latency. This information should be helpful in understanding purine metabolism of M. tuberculosis and also the metabolic activity of this important human pathogen in the persistent state.

Keywords: Keywords: mycobacterium, nucleoside analogues, MICs

Journal Article.  5780 words.  Illustrated.

Subjects: Medical Oncology ; Critical Care

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.