The bactericidal effect of lysostaphin coupled with liposomal vancomycin as a dual combating system applied directly on methicillin-resistant Staphylococcus aureus infected skin wounds in mice&nbsp

Fahimeh Hajiahmadi,1 Mohammad Yousef Alikhani,1,2 Hanifeh Shariatifar,3 Mohammad Reza Arabestani,1,2 Davoud Ahmadvand4,51Department of Microbiology, Hamadan University of Medical Sciences, Hamadan, Iran; 2Brucellosis Research Center, Faculty of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran; 3Young Researches and Elite Club, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; 4Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran; 5Department of Medical Laboratory Sciences, Faculty of Allied Medicine, Iran University of Medical Sciences, Tehran, IranBackground and aim: Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most common causes of surgical infection, and its resistance to numerous conventional antibiotics makes treatment difficult. Although vancomycin is often an effective agent for the initial therapy of MRSA, clinical failure sometimes occurs. Therefore, there is an urgent need to develop better therapies. Here, we prepared some vancomycin-loaded nanoliposomes coupled with anti-staphylococcal protein (lysostaphin) and evaluated their in vitro and in vivo efficacy as a topical MRSA therapy.Methods: Vancomycin was encapsulated in liposomes, and the coupling of lysostaphin with the surface of liposomes was carried out through cyanuric functional groups. The bactericidal efficacies and a full characterization were evaluated. To define different nanoliposomal–bacterium interactions and their bactericidal effect, flow cytometry was employed. Finally, in vivo, the topical antibacterial activity of each formulation was measured against surgical wound MRSA infection in a mouse model.Results: High encapsulation and conjugation efficiency were achieved for all formulations. All the formulations showed a significant reduction in bacterial counts (p