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Antimicrobials from a feline commensal bacterium inhibit skin infection by drug-resistant S. pseudintermedius

Methicillin-resistant Staphylococcus pseudintermedius (MRSP) is an important emerging zoonotic pathogen that causes severe skin infections. To combat infections from drug-resistant bacteria, the transplantation of commensal antimicrobial bacteria as a therapeutic has shown clinical promise. We scree...

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Detalles Bibliográficos
Autores principales: O'Neill, Alan M, Worthing, Kate A, Kulkarni, Nikhil, Li, Fengwu, Nakatsuji, Teruaki, McGrosso, Dominic, Mills, Robert H, Kalla, Gayathri, Cheng, Joyce Y, Norris, Jacqueline M, Pogliano, Kit, Pogliano, Joe, Gonzalez, David J, Gallo, Richard L
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8592530/
https://www.ncbi.nlm.nih.gov/pubmed/34664551
http://dx.doi.org/10.7554/eLife.66793
Descripción
Sumario:Methicillin-resistant Staphylococcus pseudintermedius (MRSP) is an important emerging zoonotic pathogen that causes severe skin infections. To combat infections from drug-resistant bacteria, the transplantation of commensal antimicrobial bacteria as a therapeutic has shown clinical promise. We screened a collection of diverse staphylococcus species from domestic dogs and cats for antimicrobial activity against MRSP. A unique strain (S. felis C4) was isolated from feline skin that inhibited MRSP and multiple gram-positive pathogens. Whole genome sequencing and mass spectrometry revealed several secreted antimicrobials including a thiopeptide bacteriocin micrococcin P1 and phenol-soluble modulin beta (PSMβ) peptides that exhibited antimicrobial and anti-inflammatory activity. Fluorescence and electron microscopy revealed that S. felis antimicrobials inhibited translation and disrupted bacterial but not eukaryotic cell membranes. Competition experiments in mice showed that S. felis significantly reduced MRSP skin colonization and an antimicrobial extract from S. felis significantly reduced necrotic skin injury from MRSP infection. These findings indicate a feline commensal bacterium that could be utilized in bacteriotherapy against difficult-to-treat animal and human skin infections.