Liposomal Therapy Attenuates Dermonecrosis Induced by Community-Associated Methicillin-Resistant Staphylococcus aureus by Targeting α-Type Phenol-Soluble Modulins and α-Hemolysin.

Wolfmeier, Heidi Annemarie; Mansour, Sarah C; Liu, Leo T; Pletzer, Daniel; Draeger, Annette; Babiychuk, Eduard; Hancock, Robert E W (2018). Liposomal Therapy Attenuates Dermonecrosis Induced by Community-Associated Methicillin-Resistant Staphylococcus aureus by Targeting α-Type Phenol-Soluble Modulins and α-Hemolysin. EBioMedicine, 33, pp. 211-217. Elsevier 10.1016/j.ebiom.2018.06.016

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy > Cell Biology

UniBE Contributor:

Wolfmeier, Heidi Annemarie; Draeger, Annette and Babiychuk, Eduard

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

2352-3964

Publisher:

Elsevier

Language:

English

Submitter:

Annette Draeger

Date Deposited:

21 Feb 2019 10:48

Last Modified:

23 Oct 2019 19:44

Publisher DOI:

10.1016/j.ebiom.2018.06.016

PubMed ID:

29936135

Uncontrolled Keywords:

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

BORIS DOI:

10.7892/boris.125161

URI:

https://boris.unibe.ch/id/eprint/125161

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