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Pharmaceuticals 2015, 8(4), 778-792; doi:10.3390/ph8040778

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

1
Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ 08544, USA
2
Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA
3
Rutgers Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Academic Editor: Dacheng Ren
Received: 10 August 2015 / Revised: 2 November 2015 / Accepted: 6 November 2015 / Published: 17 November 2015
(This article belongs to the Special Issue Microbial Biofilms)
View Full-Text   |   Download PDF [369 KB, uploaded 19 November 2015]   |  

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. View Full-Text
Keywords: fluoroquinolone; persistence; prophage induction; S. aureus fluoroquinolone; persistence; prophage induction; S. aureus
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MDPI and ACS Style

Sandvik, E.L.; Fazen, C.H.; Henry, T.C.; Mok, W.W.; Brynildsen, M.P. Non-Monotonic Survival of Staphylococcus aureus with Respect to Ciprofloxacin Concentration Arises from Prophage-Dependent Killing of Persisters. Pharmaceuticals 2015, 8, 778-792.

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