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Infection and Immunity, February 2003, p. 997-1000, Vol. 71, No. 2
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.2.997-1000.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

DNA Alkylation Damage as a Sensor of Nitrosative Stress in Mycobacterium tuberculosis

Steven I. Durbach,1 Burkhard Springer,2 Edith E. Machowski,1 Robert J. North,3 K. G. Papavinasasundaram,4 M. Jo Colston,4 Erik C. Böttger,2 and Valerie Mizrahi1*

MRC/NHLS/WITS Molecular Mycobacteriology Research Unit, School of Pathology, University of the Witwatersrand, and National Health Laboratory Service, Johannesburg, South Africa,1 Institute für Medizinische Mikrobiologie, Universität Zürich, Zürich, Switzerland,2 Trudeau Medical Institute, Saranac Lake, New York,3 Division of Mycobacterial Research, National Institute for Medical Research, The Ridgeway, Mill Hill, London, United Kingdom4

Received 17 December 2001/ Returned for modification 11 February 2002/ Accepted 31 October 2002

One of the cellular consequences of nitrosative stress is alkylation damage to DNA. To assess whether nitrosative stress is registered on the genome of Mycobacterium tuberculosis, mutants lacking an alkylation damage repair and reversal operon were constructed. Although hypersensitive to the genotoxic effects of N-methyl-N'-nitro-N-nitrosoguanidine in vitro, the mutants displayed no phenotype in vivo, suggesting that permeation of nitrosative stress to the level of cytotoxic DNA damage is restricted.


* Corresponding author. Mailing address: MRC/NHLS/WITS Molecular Mycobacteriology Research Unit, NHLS, P.O. Box 1038, Johannesburg 2000, South Africa. Phone: 2711-4899370. Fax: 2711-4899001. E-mail: mizrahiv{at}pathology.wits.ac.za.

Editor: S. H. E. Kaufmann


Infection and Immunity, February 2003, p. 997-1000, Vol. 71, No. 2
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.2.997-1000.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.




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