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...

Descripción completa

Detalles Bibliográficos
Autores principales: Sandvik, Elizabeth L., Fazen, Christopher H., Henry, Theresa C., Mok, Wendy W.K., Brynildsen, Mark P.
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