Zinc-substituted hydroxyapatite-bacteriophage complexes for complementary antibacterial properties

The increasing resistance of bacteria to antibiotics poses a significant threat to human health. Therefore, new treatment options, including alternative antimicrobial agents, are being sought. Taking into account that the combination of bacteriophages with antibacterial metal ions could provide a synergistic effect, as well as the extensive use of hydroxyapatite (HAp) in the development of bone implant materials, Zn-substituted HAp (ZnHAp) nanoparticles' interaction with bacteriophages was evaluated for the first time. The physicochemical and antibacterial properties of the ZnHAp nanoparticles were characterized. Pure-phase HAp nanoparticles with Zn content up to 0.74 ± 0.07 wt% were synthesized using wet chemical precipitation. The ZnHAp nanoparticles did not show antibacterial activity against Gram-negative Pseudomonas aeruginosa ( P. aeruginosa ) bacteria. In turn, the ZnHAp nanoparticles’ antibacterial activity against Gram-positive Staphylococcus aureus ( S. aureus ) bacteria depended on the Zn concentration and the incubation time - the highest efficiency was shown by the HAp nanoparticles with 0.74 ± 0.07 wt% of Zn after 72 h. P. aeruginosa and S. aureus bacteriophages retained lytic activity after incubation in the presence of the nanoparticles, showing activity against host bacteria, i.e. , a moderate titer (10 6 -10 8 PFU/mL), yet corresponding to an effective therapeutic titer both in the bacteriophage suspension and sediments after decantation. The current findings illustrated that combining lytic phages with metallic ions substituted HAp nanoparticles is a promising technique for obtaining novel biomaterials with the prevention and treatment potential of polymicrobial and biofilm infections. • Phase-pure HAp nanoparticles containing up to 0.8 wt% of Zn were synthesized. • Zn confers antibacterial activity of HAp against S. aureus . • After incubation with HAp nanoparticles, phages retain activity against host bacteria. • Phages confer antibacterial activity of HAp against S. aureus and P. aeruginosa.