The impact of agarose immobilization on the activity of lytic Pseudomonas aeruginosa phages combined with chemicals

The implementation of non-traditional antibacterials is currently one of the most intensively explored areas of modern medical and biological sciences. One of the most promising alternative strategies to combat bacterial infections is the application of lytic phages combined with established and new antibacterials. The presented study investigates the potential of agarose-based biocomposites containing lytic Pseudomonas phages (KT28, KTN4, and LUZ19), cupric ions (Cu2+), strawberry furanone (HDMF), and gentamicin (GE) as antibacterials and anti-virulent compounds for novel wound dressings. Phages (KT28, KTN4, LUZ19, and triple-phage cocktail) alone and in combination with a triple-chemical mixture (Cu + GE + HDMF) when applied as the liquid formulation caused a significant bacterial count reduction and biofilm production inhibition of clinical P. aeruginosa strains. The immobilization in the agarose scaffold significantly impaired the bioavailability and diffusion of phage particles, depending on virion morphology and targeted receptor specificity. The antibacterial potential of chemicals was also reduced by the agarose scaffold. Moreover, the Cu + GE + HDMF mixture impaired the lytic activity of phages depending on viral particles' susceptibility to cupric ion toxicity. Therefore, three administration types were tested and the optimal turned out to be the one separating antibacterials both physically and temporally. Taken together, the additive effect of phages combined with chemicals makes biocomposite a good solution for designing new wound dressings. Nevertheless, the phage utilization should involve an application of aqueous cocktails directly onto the wound, followed by chemicals immobilized in hydrogel dressings which allow for taking advantage of the antibacterial and anti-virulent effects of all components.

Automated summary

The implementation of non-traditional antibacterials, such as lytic phages combined with established and new antibacterials, is currently being extensively explored in medical and biological sciences. This study investigates the potential of agarose-based biocomposites containing phages and chemicals as antibacterials for wound dressings. The results show that the combination of phages and a triple-chemical mixture significantly reduces bacterial count and inhibits biofilm production. However, the bioavailability and diffusion of phages are impaired by the agarose scaffold, and the lytic activity of phages is affected by the chemical mixture. The optimal administration method is found to separate antibacterials both physically and temporally. Overall, the additive effect of phages and chemicals makes biocomposites a promising solution for designing new wound dressings.