Interaction between Staphylococcus Agr virulence and neutrophils regulates pathogen expansion in the skin.
Cell Host Microbe
; 29(6): 930-940.e4, 2021 06 09.
Article
em En
| MEDLINE
| ID: mdl-33852876
ABSTRACT
Staphylococcus aureus commonly infects the skin, but the host-pathogen interactions controlling bacterial growth remain unclear. S. aureus virulence is regulated by the Agr quorum-sensing system that controls factors including phenol-soluble modulins (PSMs), a group of cytotoxic peptides. We found a differential requirement for Agr and PSMα for pathogen growth in the skin. In neutrophil-deficient mice, S. aureus growth on the epidermis was unaffected, but the pathogen penetrated the dermis through mechanisms that require PSMα. In the dermis, pathogen expansion required Agr in wild-type mice, but not in neutrophil-deficient mice. Agr limited oxidative and non-oxidative killing in neutrophils by inhibiting pathogen late endosome localization and promoting phagosome escape. Unlike Agr, the SaeR/S virulence program was dispensable for growth in the epidermis and promoted dermal pathogen expansion independently of neutrophils. Thus, S. aureus growth and invasion are differentially regulated with Agr limiting intracellular killing within neutrophils to promote pathogen expansion in the dermis and subcutaneous tissue.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pele
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Infecções Estafilocócicas
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Staphylococcus aureus
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Proteínas de Bactérias
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Virulência
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Transativadores
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Neutrófilos
Limite:
Animals
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Humans
Idioma:
En
Revista:
Cell Host Microbe
Ano de publicação:
2021
Tipo de documento:
Article