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A recA-LexA-dependent pathway mediates ciprofloxacin-induced fibronectin binding in Staphylococcus aureus

Hooper, D. C.
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Published in The Journal of biological chemistry. 2004, vol. 279, no. 10, p. 9064-9071
Abstract Subinhibitory concentrations of ciprofloxacin (CPX) raise the fibronectin-mediated attachment of fluoroquinolone-resistant Staphylococcus aureus by selectively inducing fnbB coding for one of two fibronectin-binding proteins: FnBPB. To identify candidate regulatory pathway(s) linking drug exposure to up-regulation of fnbB, we disrupted the global response regulators agr, sarA, and recA in the highly quinolone-resistant strain RA1. Whereas agr and sarA mutants of RA1 exposed to CPX still displayed increased adhesion to fibronectin, the CPX-triggered response was abolished in the uvs-568 recA mutant, but was restored following complementation with wild type recA. Steady-state levels of recA and fnbB, but not fnbA, mRNA were co-coordinately increased >3-fold in CPX-exposed strain RA1. Electrophoretic mobility shift assays revealed specific binding of purified S. aureus SOS-repressor LexA to recA and fnbB, but not to fnbA or rpoB promoters. DNase I footprint analysis showed LexA binding overlapping the core promoter elements in fnbB. We conclude that activation of recA and derepression of lexA-regulated genes by CPX may represent a response to drug-induced damage that results in a novel induction of a virulence factor leading to increased bacterial tissue adherence.
Keywords Anti-Infective Agents/pharmacologyBacterial Adhesion/drug effectsBacterial Proteins/ metabolismBase SequenceCiprofloxacin/pharmacologyFibronectins/genetics/ metabolismMolecular Sequence DataPromoter Regions, GeneticProtein BindingRec A Recombinases/genetics/ metabolismSerine Endopeptidases/ metabolismStaphylococcus aureus/ metabolism
PMID: 14699158
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BISOGNANO, Carmelo et al. A recA-LexA-dependent pathway mediates ciprofloxacin-induced fibronectin binding in Staphylococcus aureus. In: The Journal of biological chemistry, 2004, vol. 279, n° 10, p. 9064-9071. doi: 10.1074/jbc.M309836200 https://archive-ouverte.unige.ch/unige:7109

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Deposited on : 2010-06-21

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