Skip Navigation



JAC Advance Access published online on April 6, 2005
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dki069
This Article
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
55/5/674    most recent
dki069v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by O'Sullivan, D. M.
Right arrow Articles by Gillespie, S. H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by O'Sullivan, D. M.
Right arrow Articles by Gillespie, S. H.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2005. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oupjournals.org
Received October 14, 2004
Revised January 19, 2005
Accepted January 22, 2004

Original article

Analysis of rpoB and pncA mutations in the published literature: an insight into the role of oxidative stress in Mycobacterium tuberculosis evolution?

Denise M. O'Sullivan 1, Timothy D. McHugh 1, and Stephen H. Gillespie 1*

1 Centre for Medical Microbiology, Department of Infection, Royal Free & University College Medical School, Royal Free Campus, University College London, Rowland Hill Street, London NW3 2PF, UK

* To whom correspondence should be addressed.
Stephen H. Gillespie, E-mail: s.gillespie{at}medsch.ucl.ac.uk


  Abstract

Introduction: It is perceived wisdom that within the host macrophage, Mycobacterium tuberculosis frequently encounters oxidative stress. Exposure of bacteria to reactive oxygen intermediates can have a mutagenic effect on the DNA. Various mutations are thought to arise as a consequence, including the oxidation of guanine residues, leading to G·C->T·A substitution, and oxidation of cytosine resulting in a G·C->A·T substitution.

Methods: We measured the relative contribution of oxidative stress by recording the percentage of single nucleotide substitutions reported in the genes rpoB and pncA that confer resistance to the antimicrobials rifampicin and pyrazinamide, respectively, and determined whether there is an excess of G·C->T·A or G·C->A·T substitutions.

Results: Out of 840 clinical isolates reported with single nucleotide mutations in the rpoB gene, 67% were G·C->A·T changes, and 3% were G·C->T·A substitutions. These figures were compared with the pncA gene, where out of 114 isolates, 30% of the single nucleotide mutations were G·C->A·T transitions and 9% were G·C->T·A changes.

Conclusions: While there is an excess of G·C->A·T changes in the rpoB gene, this was not the case in the pncA gene. Fifty-three percent of mutations within the rpoB gene were C->T mutations of the type S531L. Although this mutation gives a fitness disadvantage, the disadvantage is less than other common mutations, so it is more likely that fitness is the determinant of surviving mutations rather than oxidative stress because of the small numbers of other C->T and G->A mutations at other sites (12%). There was no evidence of oxygen free radicals damaging the guanine bases in either gene.

Keywords: M. tuberculosis; rpoB gene; pncA gene.
Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 J Antimicrob ChemotherHome page
D. M. O'Sullivan, T. D. McHugh, and S. H. Gillespie
The effect of oxidative stress on the mutation rate of Mycobacterium tuberculosis with impaired catalase/peroxidase function
J. Antimicrob. Chemother., October 1, 2008; 62(4): 709 - 712.
[Abstract] [Full Text] [PDF]

Home page
 Antimicrob. Agents Chemother.Home page
J. R. O'Connor, M. A. Galang, S. P. Sambol, D. W. Hecht, G. Vedantam, D. N. Gerding, and S. Johnson
Rifampin and Rifaximin Resistance in Clinical Isolates of Clostridium difficile
Antimicrob. Agents Chemother., August 1, 2008; 52(8): 2813 - 2817.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
H. I. M. Boshoff, X. Xu, K. Tahlan, C. S. Dowd, K. Pethe, L. R. Camacho, T.-H. Park, C.-S. Yun, D. Schnappinger, S. Ehrt, et al.
Biosynthesis and Recycling of Nicotinamide Cofactors in Mycobacterium tuberculosis: AN ESSENTIAL ROLE FOR NAD IN NONREPLICATING BACILLI
J. Biol. Chem., July 11, 2008; 283(28): 19329 - 19341.
[Abstract] [Full Text] [PDF]

Home page
 Antimicrob. Agents Chemother.Home page
P. Jureen, J. Werngren, J.-C. Toro, and S. Hoffner
Pyrazinamide Resistance and pncA Gene Mutations in Mycobacterium tuberculosis
Antimicrob. Agents Chemother., May 1, 2008; 52(5): 1852 - 1854.
[Abstract] [Full Text] [PDF]

Home page
 J Antimicrob ChemotherHome page
R. C. Y. Chan, M. Hui, E. W. C. Chan, T. K. Au, M. L. Chin, C. K. Yip, C. K. W. AuYeang, C. Y. L. Yeung, K. M. Kam, P. C. W. Yip, et al.
Genetic and phenotypic characterization of drug-resistant Mycobacterium tuberculosis isolates in Hong Kong
J. Antimicrob. Chemother., May 1, 2007; 59(5): 866 - 873.
[Abstract] [Full Text] [PDF]


Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.