Combining Bacteriophages with Other Antibacterial Agents to Combat Bacteria

Bacteriophages have been used to control bacterial growth, but so far, they have also been successfully combined with various antibacterial agents that inhibit cell wall synthesis, cell membrane function, DNA replication, transcription or translation, etc. Many combinations have shown greater activity against bacteria in comparison to individual activities of the applied agents. This phenomenon, denoted as synergy, has been firstly recorded in the 1940s for penicillin and Staphylococcus phage K combination and further widely examined during the last decade. The synergy is observed both against planktonic and biofilm embedded bacterial cells and this approach possesses many advantages, mainly because of decreased effective concentration of chemical antibacterial agents and reduction of resistance occurrence. The mechanisms of synergistic interaction has not yet been fully elucidated but probably comprise change of bacterial phenotypic properties (e.g., cell elongation, change of cell surface properties, degradation of exopolysaccharides) and elimination of phage-resistant and antibiotic-resistant mutants during combined treatment. The future studies of synergy between chemical agents and phages should overcome current shortfalls, particularly those related to methodology, as well as phage and antibiotic selection. Several studies have confirmed the phenomenon in vivo, but additional studies, including well-designed clinical trials, are necessary for therapeutic exploitation of the synergy.