Bacteriophage and Antimicrobial Peptide Combination Treatments Against Pseudomonas aeruginosa and Candida albicans
Charlton Lam 1*, Katarzyna Danis-Wlodarczyk 2, Daniel Wozniak 1,2
- The Department of Microbiology, The Ohio State University, Columbus OH, USA
- The Department of Microbial Infection & Immunity, The Ohio State University, Columbus OH, USA
Charlton Lam; lam.384@osu.edu
Pseudomonas aeruginosa and Candida albicans are opportunistic pathogens of great concern due to their broad arsenal of virulence factors and resistance to antimicrobial drugs. These pathogens are among the most common agents in hospital-acquired infections and are often co-isolated from lung and wound infections. Furthermore, mixed-species biofilm formation often plays an important role during these infections, providing additional protection against antimicrobial compounds. P. aeruginosa preferentially binds to C. albicans hyphae in mixed-species biofilms, shielding C. albicans from environmental stresses, including antimicrobial treatment. Bacteriophage (phage) therapy and antimicrobial peptides (AMPs) present as encouraging approaches as treatment against such infections. Phage therapy, however, provides limited remedy for fungal infections. There also are no known lytic viruses that infect Candida spp. Therefore, the present study aims to develop novel treatments against P. aeruginosa and Candida spp. mixed infections, using combinations of phages and antimicrobial peptides. Specifically, we analyzed phage-AMP combinations against single- and dual-species populations growing planktonically and in biofilms. We tested 4 different phages (LUZ19, PEV2, 14-1, YuA) and 7 different AMPs (chCATH-2, histatin-5, Cm-p5, AurH1, IDR-1018, human β-defensin-3, bovine lactoferricin) exhibiting antibacterial, antifungal, and/or anti-biofilm activities. First, we examined phage stability and adsorption kinetics in the presence of AMPs. Several antagonistic combinations were observed, which were excluded from further testing. Next, suitable candidates were assessed against planktonic P. aeruginosa and C. albicans cultures via lysis profile analysis, as well as their ability to degrade established single- and dual-species biofilms in vitro. We identified phage-AMP combinations with increased effectiveness against P. aeruginosa and C. albicans planktonic cultures and mixed biofilms in comparison to single phage or AMP treatments, indicating additive activity between these two types of antimicrobial agents.