Mycobacterium tuberculosis DNA repair in response to subinhibitory concentrations of ciprofloxacin.
OBJECTIVE
To investigate how the SOS response, an error-prone DNA repair pathway, is expressed following subinhibitory quinolone treatment of Mycobacterium tuberculosis.


METHODS
Genome-wide expression profiling followed by quantitative RT (qRT)-PCR was used to study the effect of ciprofloxacin on M. tuberculosis gene expression.


RESULTS
Microarray analysis showed that 16/110 genes involved in DNA protection, repair and recombination were up-regulated. There appeared to be a lack of downstream genes involved in the SOS response. qRT-PCR detected an induction of lexA and recA after 4 h and of dnaE2 after 24 h of subinhibitory treatment.


CONCLUSIONS
The pattern of gene expression observed following subinhibitory quinolone treatment differed from that induced after other DNA-damaging agents (e.g. mitomycin C). The expression of the DnaE2 polymerase response was significantly delayed following subinhibitory quinolone exposure.
O'Sullivan
D M
DM
Centre for Medical Microbiology, Department of Infection, Royal Free Campus, University College London, Rowland Hill Street, Hampstead, London NW3 2PF, UK.
Hinds
J
J
Butcher
P D
PD
Gillespie
S H
SH
McHugh
T D
TD
D000995:Antitubercular Agents / Q000494:pharmacology*; D002939:Ciprofloxacin / Q000494:pharmacology*; D004260:DNA Repair; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000502:physiology*; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013014:SOS Response, Genetics
D000995:Antitubercular Agents; D002939:Ciprofloxacin
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