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

• Type of Material: Article
• Authors: Waqas N. Chaudhry, National University of Sciences and Technology; Jennifer Concepción-Acevedo, Emory University; Taehyun Park, The University of Texas at Austin; Saadia Andleeb, National University of Sciences and Technology; James J. Bull, The University of Texas at Austin; Bruce Levin, Emory University
• Language: English
• Date: 2017-01-11
• Publisher: Public Library of Science
• Publication Version: Final Published Version
• Copyright Statement: © 2017 Chaudhry et al
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1371/journal.pone.0168615
• Title of Journal or Parent Work: PLoS ONE
• ISSN: 1932-6203
• Volume: 12
• Issue: 1
• Start Page: e0168615
• End Page: e0168615
• Grant/Funding Information: 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.; 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.
• Keywords: immunology; antibiotics; biofilms; pseudomonas aeruginosa
• Research Categories: Biology, Molecular; Biology, General

Abstract

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.