Cargando…
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...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2015
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4695809/ https://www.ncbi.nlm.nih.gov/pubmed/26593926 http://dx.doi.org/10.3390/ph8040778 |
_version_ | 1782407695877275648 |
---|---|
author | Sandvik, Elizabeth L. Fazen, Christopher H. Henry, Theresa C. Mok, Wendy W.K. Brynildsen, Mark P. |
author_facet | Sandvik, Elizabeth L. Fazen, Christopher H. Henry, Theresa C. Mok, Wendy W.K. Brynildsen, Mark P. |
author_sort | Sandvik, Elizabeth L. |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-4695809 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-46958092016-01-19 Non-Monotonic Survival of Staphylococcus aureus with Respect to Ciprofloxacin Concentration Arises from Prophage-Dependent Killing of Persisters Sandvik, Elizabeth L. Fazen, Christopher H. Henry, Theresa C. Mok, Wendy W.K. Brynildsen, Mark P. Pharmaceuticals (Basel) Article 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. MDPI 2015-11-17 /pmc/articles/PMC4695809/ /pubmed/26593926 http://dx.doi.org/10.3390/ph8040778 Text en © 2015 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Sandvik, Elizabeth L. Fazen, Christopher H. Henry, Theresa C. Mok, Wendy W.K. Brynildsen, Mark P. Non-Monotonic Survival of Staphylococcus aureus with Respect to Ciprofloxacin Concentration Arises from Prophage-Dependent Killing of Persisters |
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 | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4695809/ https://www.ncbi.nlm.nih.gov/pubmed/26593926 http://dx.doi.org/10.3390/ph8040778 |
work_keys_str_mv | AT sandvikelizabethl nonmonotonicsurvivalofstaphylococcusaureuswithrespecttociprofloxacinconcentrationarisesfromprophagedependentkillingofpersisters AT fazenchristopherh nonmonotonicsurvivalofstaphylococcusaureuswithrespecttociprofloxacinconcentrationarisesfromprophagedependentkillingofpersisters AT henrytheresac nonmonotonicsurvivalofstaphylococcusaureuswithrespecttociprofloxacinconcentrationarisesfromprophagedependentkillingofpersisters AT mokwendywk nonmonotonicsurvivalofstaphylococcusaureuswithrespecttociprofloxacinconcentrationarisesfromprophagedependentkillingofpersisters AT brynildsenmarkp nonmonotonicsurvivalofstaphylococcusaureuswithrespecttociprofloxacinconcentrationarisesfromprophagedependentkillingofpersisters |