A recA-LexA-dependent pathway mediates ciprofloxacin-induced fibronectin binding in Staphylococcus aureus.
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.
Bisognano
Carmelo
C
Division of Infectious Diseases, University Hospital, CH-1211 Geneva 14, Switzerland.
Kelley
William L
WL
Estoppey
Tristan
T
Francois
Patrice
P
Schrenzel
Jacques
J
Li
Dongmei
D
Lew
Daniel P
DP
Hooper
David C
DC
Cheung
Ambrose L
AL
Vaudaux
Pierre
P
D000890:Anti-Infective Agents / Q000494:pharmacology; D001422:Bacterial Adhesion / Q000187:drug effects; D001426:Bacterial Proteins / Q000378:metabolism*; D001483:Base Sequence; D002939:Ciprofloxacin / Q000494:pharmacology; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011938:Rec A Recombinases / Q000235:genetics / Q000378:metabolism*; D012697:Serine Endopeptidases / Q000378:metabolism*; D013211:Staphylococcus aureus / Q000378:metabolism*; D000099160:LexA Repressor Protein
D000890:Anti-Infective Agents; D001426:Bacterial Proteins; D002939:Ciprofloxacin; D005353:Fibronectins; D011938:Rec A Recombinases; D012697:Serine Endopeptidases; D000099160:LexA Repressor Protein