Friends or foes? Rapid determination of dissimilar colistin and ciprofloxacin antagonism of pseudomonas aeruginosa phages

Katarzyna M. Danis-Wlodarczyk, Alice Cai, Anna Chen, Marissa R. Gittrich, Matthew B. Sullivan, Daniel J. Wozniak, Stephen T. Abedon

Research output: Contribution to journalArticlepeer-review

Abstract

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-through-put means of assessing antibiotic antagonism of phage infection activities.

Original languageEnglish (US)
Article number1162
JournalPharmaceuticals
Volume14
Issue number11
DOIs
StatePublished - Nov 2021

Keywords

  • Antibacterial therapy
  • Bacteriophage therapy
  • Ciprofloxacin
  • Colistin
  • Phage LUZ19
  • Phage PEV2
  • Phage ΦKMV

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery

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