Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA), typified by the pulse-field type USA300, is an emerging endemic pathogen that is spreading rapidly among healthy people. CA-MRSA causes skin and soft tissue infections, life-threatening necrotizing pneumonia and sepsis, and is remarkably resistant to many antibiotics. Here we show that engineered liposomes composed of naturally occurring sphingomyelin were able to sequester cytolytic toxins secreted by USA300 and prevent necrosis of human erythrocytes, peripheral blood mononuclear cells and bronchial epithelial cells. Mass spectrometric analysis revealed the capture by liposomes of phenol-soluble modulins, α-hemolysin and other toxins. Sphingomyelin liposomes prevented hemolysis induced by pure phenol-soluble modulin-α3, one of the main cytolytic components in the USA300 secretome. In contrast, sphingomyelin liposomes harboring a high cholesterol content (66 mol/%) were unable to protect human cells from phenol-soluble modulin-α3-induced lysis, however these liposomes efficiently sequestered the potent staphylococcal toxin α-hemolysin. In a murine cutaneous abscess model, a single dose of either type of liposomes was sufficient to significantly decrease tissue dermonecrosis. Our results provide further insights into the promising potential of tailored liposomal therapy in the battle against infectious diseases.
Sphingomyelin liposomes protected human cells from necrosis induced by CA-MRSA supernatants.
Sphingomyelin liposomes sequestered purified phenol-soluble modulin α3.
Cholesterol-containing liposomes bound α-hemolysin.
Both types of liposomes, given therapeutically, attenuated dermonecrosis in a CA-MRSA murine cutaneous abscess model.
Spreading endemically among society, community-associated methicillin resistant S. aureus (CA-MRSA) predominantly causes skin and soft tissue infections but is also associated with life-threatening diseases like sepsis. The bacterial toxins phenol-soluble modulins and α-hemolysin have been demonstrated to contribute substantially to pathogenesis and success of CA-MRSA. Here we report the efficacy of liposomes composed of naturally occurring lipids in binding and neutralizing these potent toxins, thereby protecting human cells in vitro. In a murine cutaneous abscess model, liposomal treatment reduced CA-MRSA-mediated dermonecrosis. Liposomes thus represent a potential adjunctive therapy to abscess drainage and antibiotic treatment during staphylococcal abscess infections.
Keywords: Anti-toxin therapy; CA-MRSA; Dermonecrosis; Liposomes; Phenol-soluble modulins; Skin and soft tissue infections; USA300; α-Hemolysin.
Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.