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Friends or Foes? Rapid Determination of Dissimilar Colistin and Ciprofloxacin Antagonism of Pseudomonas aeruginosa Phages

Phage therapy is a century-old technique employing viruses (phages) to treat bacterial infections, and in the clinic it is often used in combination with antibiotics. Antibiotics, however, interfere with critical bacterial metabolic activities that can be required by phages. Explicit testing of anti...

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Autores principales: Danis-Wlodarczyk, Katarzyna M., Cai, Alice, Chen, Anna, Gittrich, Marissa R., Sullivan, Matthew B., Wozniak, Daniel J., Abedon, Stephen T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8624478/
https://www.ncbi.nlm.nih.gov/pubmed/34832944
http://dx.doi.org/10.3390/ph14111162
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author Danis-Wlodarczyk, Katarzyna M.
Cai, Alice
Chen, Anna
Gittrich, Marissa R.
Sullivan, Matthew B.
Wozniak, Daniel J.
Abedon, Stephen T.
author_facet Danis-Wlodarczyk, Katarzyna M.
Cai, Alice
Chen, Anna
Gittrich, Marissa R.
Sullivan, Matthew B.
Wozniak, Daniel J.
Abedon, Stephen T.
author_sort Danis-Wlodarczyk, Katarzyna M.
collection PubMed
description Phage therapy is a century-old technique employing viruses (phages) to treat bacterial infections, and in the clinic it is often used in combination with antibiotics. Antibiotics, however, interfere with critical bacterial metabolic activities that can be required by phages. Explicit testing of antibiotic antagonism of phage infection activities, though, is not a common feature of phage therapy studies. Here we use optical density-based ‘lysis-profile’ assays to assess the impact of two antibiotics, colistin and ciprofloxacin, on the bactericidal, bacteriolytic, and new-virion-production activities of three Pseudomonas aeruginosa phages. Though phages and antibiotics in combination are more potent in killing P. aeruginosa than either acting alone, colistin nevertheless substantially interferes with phage bacteriolytic and virion-production activities even at its minimum inhibitory concentration (1× MIC). Ciprofloxacin, by contrast, has little anti-phage impact at 1× or 3× MIC. We corroborate these results with more traditional measures, particularly colony-forming units, plaque-forming units, and one-step growth experiments. Our results suggest that ciprofloxacin could be useful as a concurrent phage therapy co-treatment especially when phage replication is required for treatment success. Lysis-profile assays also appear to be useful, fast, and high-throughput means of assessing antibiotic antagonism of phage infection activities.
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spelling pubmed-86244782021-11-27 Friends or Foes? Rapid Determination of Dissimilar Colistin and Ciprofloxacin Antagonism of Pseudomonas aeruginosa Phages Danis-Wlodarczyk, Katarzyna M. Cai, Alice Chen, Anna Gittrich, Marissa R. Sullivan, Matthew B. Wozniak, Daniel J. Abedon, Stephen T. Pharmaceuticals (Basel) Article Phage therapy is a century-old technique employing viruses (phages) to treat bacterial infections, and in the clinic it is often used in combination with antibiotics. Antibiotics, however, interfere with critical bacterial metabolic activities that can be required by phages. Explicit testing of antibiotic antagonism of phage infection activities, though, is not a common feature of phage therapy studies. Here we use optical density-based ‘lysis-profile’ assays to assess the impact of two antibiotics, colistin and ciprofloxacin, on the bactericidal, bacteriolytic, and new-virion-production activities of three Pseudomonas aeruginosa phages. Though phages and antibiotics in combination are more potent in killing P. aeruginosa than either acting alone, colistin nevertheless substantially interferes with phage bacteriolytic and virion-production activities even at its minimum inhibitory concentration (1× MIC). Ciprofloxacin, by contrast, has little anti-phage impact at 1× or 3× MIC. We corroborate these results with more traditional measures, particularly colony-forming units, plaque-forming units, and one-step growth experiments. Our results suggest that ciprofloxacin could be useful as a concurrent phage therapy co-treatment especially when phage replication is required for treatment success. Lysis-profile assays also appear to be useful, fast, and high-throughput means of assessing antibiotic antagonism of phage infection activities. MDPI 2021-11-15 /pmc/articles/PMC8624478/ /pubmed/34832944 http://dx.doi.org/10.3390/ph14111162 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Danis-Wlodarczyk, Katarzyna M.
Cai, Alice
Chen, Anna
Gittrich, Marissa R.
Sullivan, Matthew B.
Wozniak, Daniel J.
Abedon, Stephen T.
Friends or Foes? Rapid Determination of Dissimilar Colistin and Ciprofloxacin Antagonism of Pseudomonas aeruginosa Phages
title Friends or Foes? Rapid Determination of Dissimilar Colistin and Ciprofloxacin Antagonism of Pseudomonas aeruginosa Phages
title_full Friends or Foes? Rapid Determination of Dissimilar Colistin and Ciprofloxacin Antagonism of Pseudomonas aeruginosa Phages
title_fullStr Friends or Foes? Rapid Determination of Dissimilar Colistin and Ciprofloxacin Antagonism of Pseudomonas aeruginosa Phages
title_full_unstemmed Friends or Foes? Rapid Determination of Dissimilar Colistin and Ciprofloxacin Antagonism of Pseudomonas aeruginosa Phages
title_short Friends or Foes? Rapid Determination of Dissimilar Colistin and Ciprofloxacin Antagonism of Pseudomonas aeruginosa Phages
title_sort friends or foes? rapid determination of dissimilar colistin and ciprofloxacin antagonism of pseudomonas aeruginosa phages
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8624478/
https://www.ncbi.nlm.nih.gov/pubmed/34832944
http://dx.doi.org/10.3390/ph14111162
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