A window of opportunity to control the bacterial pathogen Pseudomonas aeruginosa combining antibiotics and phages

PLoS One. 2014 Sep 26;9(9):e106628. doi: 10.1371/journal.pone.0106628. eCollection 2014.

Abstract

The evolution of antibiotic resistance in bacteria is a global concern and the use of bacteriophages alone or in combined therapies is attracting increasing attention as an alternative. Evolutionary theory predicts that the probability of bacterial resistance to both phages and antibiotics will be lower than to either separately, due for example to fitness costs or to trade-offs between phage resistance mechanisms and bacterial growth. In this study, we assess the population impacts of either individual or combined treatments of a bacteriophage and streptomycin on the nosocomial pathogen Pseudomonas aeruginosa. We show that combining phage and antibiotics substantially increases bacterial control compared to either separately, and that there is a specific time delay in antibiotic introduction independent of antibiotic dose, that minimizes both bacterial density and resistance to either antibiotics or phage. These results have implications for optimal combined therapeutic approaches.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Anti-Bacterial Agents / therapeutic use
  • Bacteriophages / physiology*
  • Drug Resistance, Bacterial
  • Humans
  • Pseudomonas Infections / drug therapy
  • Pseudomonas Infections / prevention & control
  • Pseudomonas Phages
  • Pseudomonas aeruginosa / drug effects*
  • Pseudomonas aeruginosa / growth & development
  • Pseudomonas aeruginosa / virology*

Substances

  • Anti-Bacterial Agents

Grant support

This work was supported by the McDonnell Foundation (JSMF 220020294/SCS-Research Award), Agence National de la Recherche for funding (‘EVORANGE’ (ANR-09-PEXT-011) and ‘EvolStress’ (ANR-09-BLAN-099-01)), Erasmus Mundus Masters Programme and the CONACyT. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.