Non-Monotonic Survival of Staphylococcus aureus with Respect to Ciprofloxacin Concentration Arises from Prophage-Dependent Killing of Persisters. Author Elizabeth Sandvik, Christopher Fazen, Theresa Henry, Wendy Mok, Mark Brynildsen Publication Year 2015 Type Journal Article Abstract Staphylococcus aureus is a notorious pathogen with a propensity to cause chronic, non-healing wounds. Bacterial persisters have been implicated in the recalcitrance of S. aureus infections, and this motivated us to examine the persistence of S. aureus to ciprofloxacin, a quinolone antibiotic. Upon treatment of exponential phase S. aureus with ciprofloxacin, we observed that survival was a non-monotonic function of ciprofloxacin concentration. Maximal killing occurred at 1 µg/mL ciprofloxacin, which corresponded to survival that was up to ~40-fold lower than that obtained with concentrations ≥ 5 µg/mL. Investigation of this phenomenon revealed that the non-monotonic response was associated with prophage induction, which facilitated killing of S. aureus persisters. Elimination of prophage induction with tetracycline was found to prevent cell lysis and persister killing. We anticipate that these findings may be useful for the design of quinolone treatments. Journal Pharmaceuticals (Basel) Volume 8 Issue 4 Pages 778-92 Date Published 2015 Nov 17 ISSN Number 1424-8247 DOI 10.3390/ph8040778 Alternate Journal Pharmaceuticals (Basel) PMCID PMC4695809 PMID 26593926 PubMedPubMed CentralGoogle ScholarBibTeXEndNote X3 XML