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Author Notes:

Correspondence: Bruce Levin E-mail: blevin@emory.edu

We thank Joanna Goldberg for proving bacterial strains, Nina Walker for help in isolating the NP phage, Ian J. Molineux for his guidance in obtaining and analyzing the phage genome sequences, and John Varga and Ashley Renee Cross for their guidance to identify phage receptors.

We are grateful to Soo Min Kang and Joung Yun Choi for superb help in preparing media and other materials need for this study, as well as Young Wook ‘Justin’ Kim and James Dickey for their comments on a draft of this manuscript.

The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.


Research Funding:

National Institute of General Medical Sciences GM091875 to Bruce R. Levin. National Institute of Allergy and Infectious Diseases R21AI121685 to James J. Bull. College of Science at the Georgia Insitute of Technology to .

National Institute of Allergy and Infectious Diseases R21AI121685 to James J. Bull.

College of Science at the Georgia Insitute of Technology to National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, College of Science at the Georgia Insitute of Technology.


  • pseudomonas aeruginosa
  • immunology
  • antibiotics
  • biofilms

Synergy and Order Effects of Antibiotics and Phages in Killing Pseudomonas aeruginosa Biofilms

Journal Title:



Volume 12, Number 1


, Pages e0168615-e0168615

Type of Work:

Article | Final Publisher PDF


In contrast to planktonic cells, bacteria imbedded biofilms are notoriously refractory to treatment by antibiotics or bacteriophage (phage) used alone. Given that the mechanisms of killing differ profoundly between drugs and phages, an obvious question is whether killing is improved by combining antibiotic and phage therapy. However, this question has only recently begun to be explored. Here, in vitro biofilm populations of Pseudomonas aeruginosa PA14 were treated singly and with combinations of two phages and bactericidal antibiotics of five classes. By themselves, phages and drugs commonly had only modest effects in killing the bacteria. However some phage-drug combinations reduced bacterial densities to well below that of the best single treatment; in some cases, bacterial densities were reduced even below the level expected if both agents killed independently of each other (synergy). Furthermore, there was a profound order effect in some cases: treatment with phages before drugs achieved maximum killing. Combined treatment was particularly effective in killing in Pseudomonas biofilms grown on layers of cultured epithelial cells. Phages were also capable of limiting the extent to which minority populations of bacteria resistant to the treating antibiotic ascend. The potential of combined antibiotic and phage treatment of biofilm infections is discussed as a realistic way to evaluate and establish the use of bacteriophage for the treatment of humans.

Copyright information:

© 2017 Chaudhry et al

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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