title: Induction of fibronectin adhesins in quinolone-resistant Staphylococcus aureus by subinhibitory levels of ciprofloxacin or by sigma B transcription factor activity is mediated by two separate pathways.
abstract: We recently reported on the involvement of a RecA-LexA-dependent pathway in the ciprofloxacin-triggered upregulation of fibronectin-binding proteins (FnBPs) by fluoroquinolone-resistant Staphylococcus aureus. The potential additional contribution of the transcription factor sigma B (SigB) to the ciprofloxacin-triggered upregulation of FnBPs was studied in isogenic mutants of fluoroquinolone-resistant strain RA1 (a topoisomerase IV gyrase double mutant of S. aureus NCTC strain 8325), which exhibited widely different levels of SigB activity, as assessed by quantitative reverse transcription-PCR of their respective sigB and SigB-dependent asp23 transcript levels. These mutants were Tn551 insertion sigB strain TE1 and rsbU(+) complemented strain TE2, which exhibited a wild-type SigB operon. Levels of FnBP surface display and fibronectin-mediated adhesion were lower in sigB mutant TE1 or higher in the rsbU(+)-restored strain TE2 compared to their sigB(+) but rsbU parent, strain RA1, exhibiting low levels of SigB activity. Steady-state fnbA and fnbB transcripts levels were similar in strains TE1 and RA1 but increased by 4- and 12-fold, respectively, in strain TE2 compared to those in strain RA1. In contrast, fibronectin-mediated adhesion of strains TE1, RA1, and TE2 was similarly enhanced by growth in the presence of one-eighth the MIC of ciprofloxacin, which led to a significantly higher increase in their fnbB transcript levels compared to the increase in their fnbA transcript levels. Increased SigB levels led to a significant reduction in agr RNAIII; in contrast, it led to a slight increase in sarA transcript levels. In conclusion, upregulation of FnBPs by increased SigB levels and ciprofloxacin exposure in fluoroquinolone-resistant S. aureus occurs via independent pathways whose concerted actions may significantly promote bacterial adhesion and colonization.
authors.affiliation: Service of Infectious Diseases, University Hospitals of Geneva, Geneva, Switzerland.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Li
authors.forename: Adriana
authors.initials: A
authors.lastname: Renzoni
authors.forename: Tristan
authors.initials: T
authors.lastname: Estoppey
authors.forename: Carmelo
authors.initials: C
authors.lastname: Bisognano
authors.forename: Patrice
authors.initials: P
authors.lastname: Francois
authors.forename: William L
authors.initials: WL
authors.lastname: Kelley
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Lew
authors.forename: Jacques
authors.initials: J
authors.lastname: Schrenzel
authors.forename: Pierre
authors.initials: P
authors.lastname: Vaudaux
mesh_terms: D018829:Adhesins, Bacterial / Q000235:genetics; D001422:Bacterial Adhesion / Q000187:drug effects*; D001426:Bacterial Proteins / Q000235:genetics / Q000502:physiology*; D002939:Ciprofloxacin / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial; D005353:Fibronectins / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012808:Sigma Factor / Q000502:physiology*; D013211:Staphylococcus aureus / Q000187:drug effects*; D015534:Trans-Activators / Q000235:genetics
chemical_list: D018829:Adhesins, Bacterial; D001426:Bacterial Proteins; D005353:Fibronectins; C088021:SarA protein, bacterial; C079011:SigB protein, Bacteria; D012808:Sigma Factor; D015534:Trans-Activators; C078635:fibronectin-binding proteins, bacterial; D002939:Ciprofloxacin
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