Bacteriophage–Ciprofloxacin combination effectiveness depends on Staphylococcus aureus–Candida albicans dual-species communities’ growth model

Alternative therapies against multidrug-resistant bacteria are widely investigated in the postantibiotic era. Polymicrobial biofilms formed by two or more species of bacteria or fungi pose an additional threat. The removal of such complex communities requires more effort and a multidirectional approach. In this study, the effectiveness of two bacteriophages vB_SauM-A (A) and vB_SauM-D (D) combined with ciprofloxacin was used to combat Staphylococcus aureus in the presence of Candida albicans both in liquid culture and biofilm. The results showed that phage-antibiotic synergy (PAS) led to the complete removal of S. aureus in liquid culture without bacterial population regrowth after 24 hours, and C. albicans enhanced this therapeutic effect. In a biofilm assay, C. albicans presence caused a decrease of bacterial eradication and a reduction of biofilmspecific activity (BSA). However, the strong effect of PAS was observed both in mono- and dual-species biofilm. Usage of phages and ciprofloxacin (1 mg/L) caused a 90% reduction of BSA of mono-species biofilm and 69% of dual-species biofilm. Phages alone resulted in a decrease of 71% and 48%, and ciprofloxacin (1 mg/L) alone resulted in 45% and 23% reduction, respectively. The influence of C. albicans on the PAS effect against S. aureus presented in this study was not previously investigated.