Mycobacterium tuberculosis DNA repair in response to subinhibitory concentrations of ciprofloxacin.
OBJECTIVES: 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.
Item Type | Article |
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Keywords | PSEUDOMONAS-AERUGINOSA, PULMONARY TUBERCULOSIS, STAPHYLOCOCCUS-AUREUS, GENE-EXPRESSION, SOS RESPONSE, RESISTANCE, FLUOROQUINOLONES, 4-QUINOLONES, INDUCTION, SURVIVAL, Antitubercular Agents, pharmacology, Ciprofloxacin, pharmacology, DNA Repair, Gene Expression Profiling, Gene Expression Regulation, Bacterial, Genes, Bacterial, Mycobacterium tuberculosis, drug effects, physiology, Oligonucleotide Array Sequence Analysis, Reverse Transcriptase Polymerase Chain Reaction, SOS Response (Genetics) |
ISI | 260975500006 |