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

Bisognano, Carmelo; Kelley, William; Estoppey, Tristan; Francois, Patrice; Schrenzel, Jacques; Li, Dongmei; Lew, Daniel Pablo; Hooper, D. C.; Cheung, Ambrose L.; Vaudaux, Pierre

doi:10.1074/jbc.M309836200

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Title		A recA-LexA-dependent pathway mediates ciprofloxacin-induced fibronectin binding in Staphylococcus aureus
Authors		Bisognano, Carmelo Kelley, William Estoppey, Tristan Francois, Patrice Schrenzel, Jacques Li, Dongmei Lew, Daniel Pablo Hooper, D. C. Cheung, Ambrose L. Vaudaux, Pierre show all authors [1 - 10]
Published in		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/pharmacology — Bacterial Adhesion/drug effects — Bacterial Proteins/ metabolism — Base Sequence — Ciprofloxacin/pharmacology — Fibronectins/genetics/ metabolism — Molecular Sequence Data — Promoter Regions, Genetic — Protein Binding — Rec A Recombinases/genetics/ metabolism — Serine Endopeptidases/ metabolism — Staphylococcus aureus/ metabolism
Identifiers		DOI: 10.1074/jbc.M309836200 PMID: 14699158
Full text		Article - Limited access to UNIGE Other version: http://www.jbc.org/content/279/10/9064.full.pdf
Structures		Faculté de médecine / Section de médecine clinique / Département de médecine
Citation (ISO format)		BISOGNANO, Carmelo et al. A recA-LexA-dependent pathway mediates ciprofloxacin-induced fibronectin binding in Staphylococcus aureus. In: Journal of Biological Chemistry, 2004, vol. 279, n° 10, p. 9064-9071. doi: 10.1074/jbc.M309836200 https://archive-ouverte.unige.ch/unige:7109