DNA alkylation damage as a sensor of nitrosative stress in Mycobacterium tuberculosis.
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.
Durbach
Steven I
SI
MRC/NHLS/WITS Molecular Mycobacteriology Research Unit, School of Pathology, University of the Witwatersrand, and National Health Laboratory Service, Johannesburg, South Africa.
Springer
Burkhard
B
Machowski
Edith E
EE
North
Robert J
RJ
Papavinasasundaram
K G
KG
Colston
M Jo
MJ
Böttger
Erik C
EC
Mizrahi
Valerie
V
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
D004269:DNA, Bacterial; D009566:Nitrates; D008769:Methylnitronitrosoguanidine; D009565:Nitrate Reductases