Combinations of Bacteriophage Are Efficacious against Multidrug-Resistant Pseudomonas aeruginosa and Enhance Sensitivity to Carbapenem Antibiotics

Author:

Kovacs Christopher J.12,Rapp Erika M.1,Rankin William R.1,McKenzie Sophia M.1,Brasko Brianna K.1,Hebert Katherine E.1,Bachert Beth A.1ORCID,Kick Andrew R.1ORCID,Burpo F. John1ORCID,Barnhill Jason C.1

Affiliation:

1. United States Military Academy, West Point, NY 10996, USA

2. Defense Threat Reduction Agency, Fort Belvoir, VA 22060, USA

Abstract

The Gram-negative ESKAPE bacterium Pseudomonas aeruginosa has become a pathogen of serious concern due its extensive multi-drug resistance (MDR) profile, widespread incidences of hospital-acquired infections throughout the United States, and high occurrence in wound infections suffered by warfighters serving abroad. Bacteriophage (phage) therapy has received renewed attention as an alternative therapeutic option against recalcitrant bacterial infections, both as multi-phage cocktails and in combination with antibiotics as synergistic pairings. Environmental screening and phage enrichment has yielded three lytic viruses capable of infecting the MDR P. aeruginosa strain PAO1. Co-administration of each phage with the carbapenem antibiotics ertapenem, imipenem, and meropenem generated enhanced overall killing of bacteria beyond either phage or drug treatments alone. A combination cocktail of all three phages was completely inhibitory to growth, even without antibiotics. The same 3× phage cocktail also disrupted PAO1 biofilms, reducing biomass by over 75% compared to untreated biofilms. Further, the phage cocktail demonstrated broad efficacy as well, capable of infecting 33 out of 100 diverse clinical isolate strains of P. aeruginosa. Together, these results indicate a promising approach for designing layered medical countermeasures to potentiate antibiotic activity and possibly overcome resistance against recalcitrant, MDR bacteria such as P. aeruginosa. Combination therapy, either by synergistic phage-antibiotic pairings, or by phage cocktails, presents a means of controlling mutations that can allow for bacteria to gain a competitive edge.

Funder

Defense Threat Reduction Agency (DTRA) under the Service Academy Research Initiative

Army Research Office through a National Research Council Fellow program

Publisher

MDPI AG

Reference52 articles.

1. Gordillo Altamirano, F.L., and Barr, J.J. (2019). Phage Therapy in the Postantibiotic Era. Clin. Microbiol. Rev., 32.

2. The Science of Antibiotic Discovery;Lewis;Cell,2020

3. Iskandar, K., Murugaiyan, J., Hammoudi Halat, D., Hage, S.E., Chibabhai, V., Adukkadukkam, S., Roques, C., Molinier, L., Salameh, P., and Van Dongen, M. (2022). Antibiotic Discovery and Resistance: The Chase and the Race. Antibiotics, 11.

4. World Health Organization (2021). 2020 Antibacterial Agents in Clinical and Preclinical Development: An Overview and Analysis, World Health Organization.

5. Centers for Disease Control and Prevention (2019). Antibiotic Resistance Threats in the United States, 2019, Centers for Disease Control and Prevention.

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