Mycobacterium tuberculosis DNA repair in response to subinhibitory concentrations of ciprofloxacin

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Abstract

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.

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