Non-Monotonic Survival of Staphylococcus aureus with Respect to Ciprofloxacin Concentration Arises from Prophage-Dependent Killing of Persisters
| Autor: | Christopher H. Fazen, Wendy W. K. Mok, Theresa C. Henry, Elizabeth L. Sandvik, Mark P. Brynildsen |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
prophage induction
medicine.drug_class Tetracycline lcsh:Medicine lcsh:RS1-441 Pharmaceutical Science Biology fluoroquinolone medicine.disease_cause Article Microbiology Persistence (computer science) lcsh:Pharmacy and materia medica 03 medical and health sciences Quinolone antibiotic Drug Discovery medicine Pathogen Prophage 030304 developmental biology 0303 health sciences 030306 microbiology lcsh:R persistence S. aureus Quinolone Virology 3. Good health Ciprofloxacin Staphylococcus aureus Molecular Medicine medicine.drug |
| Zdroj: | Pharmaceuticals, Vol 8, Iss 4, Pp 778-792 (2015) Pharmaceuticals Volume 8 Issue 4 Pages 778-792 |
| ISSN: | 1424-8247 |
| DOI: | 10.3390/ph8040778 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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