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Forschungsdatenbank PMU-SQQUID

Liposomal Therapy Attenuates Dermonecrosis Induced by Community-Associated Methicillin-Resistant Staphylococcus aureus by Targeting α-Type Phenol-Soluble Modulins and α-Hemolysin.
Wolfmeier, H; Mansour, SC; Liu, LT; Pletzer, D; Draeger, A; Babiychuk, EB; Hancock, REW;
EBioMedicine. 2018; 33: -217.
Originalarbeiten (Zeitschrift)

PMU-Autor/inn/en

Wolfmeier Heidi

Abstract

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.


Useful keywords (using NLM MeSH Indexing)

Animals

Bacterial Proteins/antagonists*

inhibitors*

Cell Line

Community-Acquired Infections

Disease Models, Animal

Hemolysin Proteins/antagonists*

inhibitors

Humans

Liposomes

Methicillin-Resistant Staphylococcus aureus/drug effects

Methicillin-Resistant Staphylococcus aureus/metabolism*

Mice

Necrosis

Sphingomyelins/administration*

dosage*

Sphingomyelins/pharmacology

Staphylococcal Skin Infections/therapy*

Treatment Outcome


Find related publications in this database (Keywords)

Liposomes
Anti-toxin therapy
CA-MRSA
USA300
Skin and soft tissue infections
Phenol-soluble modulins
alpha-Hemolysin
Dermonecrosis