title: DNA alkylation damage as a sensor of nitrosative stress in Mycobacterium tuberculosis.
abstract: 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.
authors.affiliation: MRC/NHLS/WITS Molecular Mycobacteriology Research Unit, School of Pathology, University of the Witwatersrand, and National Health Laboratory Service, Johannesburg, South Africa.
authors.forename: Steven I
authors.initials: SI
authors.lastname: Durbach
authors.forename: Burkhard
authors.initials: B
authors.lastname: Springer
authors.forename: Edith E
authors.initials: EE
authors.lastname: Machowski
authors.forename: Robert J
authors.initials: RJ
authors.lastname: North
authors.forename: K G
authors.initials: KG
authors.lastname: Papavinasasundaram
authors.forename: M Jo
authors.initials: MJ
authors.lastname: Colston
authors.forename: Erik C
authors.initials: EC
authors.lastname: Böttger
authors.forename: Valerie
authors.initials: V
authors.lastname: Mizrahi
mesh_terms: D000478:Alkylation; D000818:Animals; D004249:DNA Damage; D004269:DNA, Bacterial / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D008769:Methylnitronitrosoguanidine / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000235:genetics* / Q000472:pathogenicity / Q000502:physiology*; D009565:Nitrate Reductases / Q000378:metabolism*; D009566:Nitrates / Q000378:metabolism; D015538:Nitrosation; D014397:Tuberculosis, Pulmonary / Q000382:microbiology; D014774:Virulence
chemical_list: D004269:DNA, Bacterial; D009566:Nitrates; D008769:Methylnitronitrosoguanidine; D009565:Nitrate Reductases