Jodie Morris1,2, Natasha Kelly3, Lisa Elliott4, Andrea Grant1, Matthew Wilkinson1, Kaushik Hazratwala1, Peter McEwen1. 1. 1 Orthopaedic Research Institute of Queensland , Townsville, Australia . 2. 2 College of Medicine, Division of Tropical Health and Medicine, James Cook University , Townsville, Australia . 3. 3 College of Public Health Medical and Veterinary Sciences, Division of Tropical Health and Medicine, James Cook University , Townsville, Australia . 4. 4 AusPhage Pty Ltd , Townsville, Australia .
Abstract
BACKGROUND: Despite significant advancements in surgical protocols and biomaterials for orthopedics, peri-prosthetic joint infection (PJI) remains a leading cause of implant failure. Staphylococcus aureus nasal colonization is an established risk factor for PJI, with methicillin-sensitive S. aureus a leading cause of orthopedic implant-related infections. The purpose of these in vitro studies was to investigate the antibacterial activity of a tailored bacteriophage cocktail against planktonic and biofilm-associated S. aureus. METHODS: The S. aureus strains (n = 30) were screened for their susceptibility to a library of S. aureus-specific bacteriophage (n = 31). Five bacteriophage preparations that demonstrated bactericidal activity against >90% of S. aureus strains tested were combined as a StaPhage cocktail and assessed for their antibacterial activity toward planktonic and biofilm-associated S. aureus, with biofilms established on three-dimensional-printed porous titanium scaffolds. RESULTS: StaPhage treatment immediately after bacterial inoculation inhibited growth of S. aureus by >98% in eight hour cultures when multiplicity of infection of phages to bacteria was greater than 1:1 (p < 0.01). Viable bacterial numbers within biofilms on titanium surfaces were significantly reduced (6.8 log10 to 6.2 log10 colony forming units [CFU]; p < 0.01) after exposure to the StaPhage cocktail, in vitro. No significant reduction was observed in biofilms exposed to 100 times the minimal inhibitory concentration of cefazolin (log10 6.81 CFU). CONCLUSIONS: Combined, these data demonstrate the in vitro efficacy of S. aureus-specific bacteriophage cocktails against S. aureus growing on porous titanium and warrant further in vivo studies in a clinically relevant animal model to evaluate the potential application of bacteriophage in the management of PJI caused by S. aureus.
BACKGROUND: Despite significant advancements in surgical protocols and biomaterials for orthopedics, peri-prosthetic joint infection (PJI) remains a leading cause of implant failure. Staphylococcus aureus nasal colonization is an established risk factor for PJI, with methicillin-sensitive S. aureus a leading cause of orthopedic implant-related infections. The purpose of these in vitro studies was to investigate the antibacterial activity of a tailored bacteriophage cocktail against planktonic and biofilm-associated S. aureus. METHODS: The S. aureus strains (n = 30) were screened for their susceptibility to a library of S. aureus-specific bacteriophage (n = 31). Five bacteriophage preparations that demonstrated bactericidal activity against >90% of S. aureus strains tested were combined as a StaPhage cocktail and assessed for their antibacterial activity toward planktonic and biofilm-associated S. aureus, with biofilms established on three-dimensional-printed porous titanium scaffolds. RESULTS: StaPhage treatment immediately after bacterial inoculation inhibited growth of S. aureus by >98% in eight hour cultures when multiplicity of infection of phages to bacteria was greater than 1:1 (p < 0.01). Viable bacterial numbers within biofilms on titanium surfaces were significantly reduced (6.8 log10 to 6.2 log10 colony forming units [CFU]; p < 0.01) after exposure to the StaPhage cocktail, in vitro. No significant reduction was observed in biofilms exposed to 100 times the minimal inhibitory concentration of cefazolin (log10 6.81 CFU). CONCLUSIONS: Combined, these data demonstrate the in vitro efficacy of S. aureus-specific bacteriophage cocktails against S. aureus growing on porous titanium and warrant further in vivo studies in a clinically relevant animal model to evaluate the potential application of bacteriophage in the management of PJI caused by S. aureus.
Authors: Wenhai Zhang; Yue Guo; Mitchell Kuss; Wen Shi; Amy L Aldrich; Jason Untrauer; Tammy Kielian; Bin Duan Journal: Tissue Eng Part B Rev Date: 2019-05-15 Impact factor: 6.389
Authors: Edison J Cano; Katherine M Caflisch; Paul L Bollyky; Jonas D Van Belleghem; Robin Patel; Joseph Fackler; Michael J Brownstein; Bri'Anna Horne; Biswajit Biswas; Matthew Henry; Francisco Malagon; David G Lewallen; Gina A Suh Journal: Clin Infect Dis Date: 2021-07-01 Impact factor: 9.079
Authors: Jodie L Morris; Hayley L Letson; Andrea Grant; Matthew Wilkinson; Kaushik Hazratwala; Peter McEwen Journal: Biol Open Date: 2019-09-18 Impact factor: 2.422
Authors: Jodie L Morris; Hayley L Letson; Lisa Elliott; Andrea L Grant; Matthew Wilkinson; Kaushik Hazratwala; Peter McEwen Journal: PLoS One Date: 2019-12-26 Impact factor: 3.240