Non-Monotonic Survival of Staphylococcus aureus with Respect to Ciprofloxacin Concentration Arises from Prophage-Dependent Killing of Persisters.

TitleNon-Monotonic Survival of Staphylococcus aureus with Respect to Ciprofloxacin Concentration Arises from Prophage-Dependent Killing of Persisters.
Publication TypeJournal Article
Year of Publication2015
AuthorsSandvik, EL, Fazen, CH, Henry, TC, Mok, WWK, Brynildsen, MP
JournalPharmaceuticals (Basel)
Volume8
Issue4
Pagination778-92
Date Published2015 Nov 17
ISSN1424-8247
Abstract

<p>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. </p>

DOI10.3390/ph8040778
Alternate JournalPharmaceuticals (Basel)
PubMed ID26593926
PubMed Central IDPMC4695809
Grant ListF30 AI114163 / AI / NIAID NIH HHS / United States