Non-Monotonic Survival of Staphylococcus aureus with Respect to Ciprofloxacin Concentration Arises from Prophage-Dependent Killing of Persisters
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 t...
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| Format: | Article |
| Language: | English |
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MDPI AG
2015-11-01
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| Series: | Pharmaceuticals |
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| Online Access: | http://www.mdpi.com/1424-8247/8/4/778 |
| _version_ | 1819076784116727808 |
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| author | Elizabeth L. Sandvik Christopher H. Fazen Theresa C. Henry Wendy W.K. Mok Mark P. Brynildsen |
| author_facet | Elizabeth L. Sandvik Christopher H. Fazen Theresa C. Henry Wendy W.K. Mok Mark P. Brynildsen |
| author_sort | Elizabeth L. Sandvik |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-21T18:46:48Z |
| format | Article |
| id | doaj.art-02b1e6020b2d440886420ca25b1e9e47 |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-12-21T18:46:48Z |
| publishDate | 2015-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-02b1e6020b2d440886420ca25b1e9e472022-12-21T18:53:52ZengMDPI AGPharmaceuticals1424-82472015-11-018477879210.3390/ph8040778ph8040778Non-Monotonic Survival of Staphylococcus aureus with Respect to Ciprofloxacin Concentration Arises from Prophage-Dependent Killing of PersistersElizabeth L. Sandvik0Christopher H. Fazen1Theresa C. Henry2Wendy W.K. Mok3Mark P. Brynildsen4Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ 08544, USADepartment of Chemical and Biological Engineering, Princeton University, Princeton, NJ 08544, USADepartment of Molecular Biology, Princeton University, Princeton, NJ 08544, USADepartment of Chemical and Biological Engineering, Princeton University, Princeton, NJ 08544, USADepartment of Chemical and Biological Engineering, Princeton University, Princeton, NJ 08544, USAStaphylococcus 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.http://www.mdpi.com/1424-8247/8/4/778fluoroquinolonepersistenceprophage inductionS. aureus |
| spellingShingle | Elizabeth L. Sandvik Christopher H. Fazen Theresa C. Henry Wendy W.K. Mok Mark P. Brynildsen Non-Monotonic Survival of Staphylococcus aureus with Respect to Ciprofloxacin Concentration Arises from Prophage-Dependent Killing of Persisters Pharmaceuticals fluoroquinolone persistence prophage induction S. aureus |
| title | Non-Monotonic Survival of Staphylococcus aureus with Respect to Ciprofloxacin Concentration Arises from Prophage-Dependent Killing of Persisters |
| title_full | Non-Monotonic Survival of Staphylococcus aureus with Respect to Ciprofloxacin Concentration Arises from Prophage-Dependent Killing of Persisters |
| title_fullStr | Non-Monotonic Survival of Staphylococcus aureus with Respect to Ciprofloxacin Concentration Arises from Prophage-Dependent Killing of Persisters |
| title_full_unstemmed | Non-Monotonic Survival of Staphylococcus aureus with Respect to Ciprofloxacin Concentration Arises from Prophage-Dependent Killing of Persisters |
| title_short | Non-Monotonic Survival of Staphylococcus aureus with Respect to Ciprofloxacin Concentration Arises from Prophage-Dependent Killing of Persisters |
| title_sort | non monotonic survival of staphylococcus aureus with respect to ciprofloxacin concentration arises from prophage dependent killing of persisters |
| topic | fluoroquinolone persistence prophage induction S. aureus |
| url | http://www.mdpi.com/1424-8247/8/4/778 |
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