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Phage-antibiotic combinations to control Pseudomonas aeruginosa-Candida two-species biofilms

Phage-antibiotic combinations to treat bacterial infections are gaining increased attention due to the synergistic effects often observed when applying both components together. This synergy has also been observed for bacteria embedded in biofilms as many phages are capable of degrading the heterogeneous material, often preventing antibiotic compounds from reaching the embedded bacteria. Most studies however focus on a single pathogen, although in many clinical cases multiple species are present at the site of infection. The aim of this study was to investigate the anti-biofilm activity of phage-antibiotic/antifungal combinations on single- and dual-species biofilms formed by the bacterium P. aeruginosa and the fungal pathogen Candida albicans, two microorganisms commonly found together in cystic fibrosis patients. The Pseudomonas phage Motto in combination with ciprofloxacin had significant anti-biofilm activity in disintegrating 24-hour-old pseudomonal biofilms. Also, other antibiotic combinations, such as cefotaxime, gentamicin, meropenem and tetracycline showed substantial effects on biofilms. We then compared biofilms formed by P. aeruginosa alone with the dual-species biofilms formed by bacteria and C. albicans. Here, we found that the phage together with the antifungal fluconazole was active against 6-hour-old dual-species biofilms but showed only negligible activity against 24-hour-old biofilms. Similarly, the combination of antibacterial compounds together with the phage showed no synergistic effects on biofilms formed by P. aeruginosa and C. albicans. This study lays the first foundation for potential therapeutic approaches to treat infections caused by bacteria and fungi using phage-antibiotic combinations.