<p>The bactericidal effect of lysostaphin coupled with liposomal vancomycin as a dual combating system applied directly on methicillin-resistant <em>Staphylococcus aureus</em> infected skin wounds in mice </p>

Abstract

Background 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< 0.05). The targeted liposomes more effectively suppress bacterial infection in vitro and in vivo relative to equivalent doses of untargeted vancomycin liposome. The flow cytometry results confirmed liposome–bacterium interactions, which increased during the incubation time. The maximum binding rate and the bactericidal effect were significantly higher in targeted liposomes ( p< 0.05) compared with control liposomes. Conclusion Our data suggest a novel nano-vehicle (lysostaphin-conjugated coupled liposomal vancomycin) which could be used as a great topical antimicrobial construct for treatment of MRSA skin infections.

Reduced Growth of Staphylococcus aureus Under High Glucose Conditions Is Associated With Decreased Pentaglycine Expression

“…Lysostaphin shows rapid bactericidal activity against methicillin-susceptible and -resistant strains of S. aureus, with minimum inhibitory concentrations (MICs) ranging from 0.03 to 2 µg/mL, as determined using an agar dilution assay (Yang et al, 2007). Recent studies have reported that lysostaphin combined with other agents, such as LL-37 peptide, liposomal vancomycin, and nisin, are effective against S. aureus infection (Ceotto-Vigoder et al, 2016;Hajiahmadi et al, 2019;Sadeghi et al, 2019). However, the MIC values of lysostaphin are greatly increased by serial subculture (Gutierrez et al, 2020).…”

Liposomes as Antibiotic Delivery Systems: A Promising Nanotechnological Strategy against Antimicrobial Resistance

“…This targeted approach enabled the immobilization of the pathogen, disrupting its cell wall and releasing the antibiotic within bacteria. Lysostaphin conjugated at liposomes surface displayed higher binding rate and bacterial effect than non-conjugated liposomes [ 70 ].…”

Nanobiosystems for Antimicrobial Drug-Resistant Infections

“…The encapsulation of VAN into LIPs improved its antistaphylococcal activity in vitro and in vivo compared to free drug injections [ 41 ]. In an in vivo study (murine model), PEGylated VAN LIPs significantly prolonged the drug blood circulation time and increased the drug deposition in lungs, liver and spleen, while reducing the drug concentration in kidneys and thereby its nephrotoxicity [ 42 , 43 ]. Bacterial toxins were used to activate drug release from VAN-LIPs that were stabilized with gold NPs, and the LIP-encapsulated VAN was released within 24 h when in the presence of MRSA bacteria, leading to bacterial growth inhibition [ 44 ].…”

“…VAN-loaded LIPs coupled with lysostaphin as the targeting ligand and the targeted LIPs suppressed bacterial infection in vitro and in vivo more effectively than equal doses of untargeted LIPs [ 43 ].…”