Poorly Cross-Linked Peptidoglycan in MRSA Due to mecA Induction Activates the Inflammasome and Exacerbates Immunopathology.
Cell Host Microbe
; 18(5): 604-12, 2015 Nov 11.
Article
em En
| MEDLINE
| ID: mdl-26567511
ABSTRACT
Methicillin-resistant S. aureus (MRSA) is a leading health problem. Compared to methicillin-sensitive S. aureus, MRSA infections are associated with greater morbidity and mortality, but the mechanisms underlying MRSA pathogenicity are unclear. Here we show that the protein conferring ß-lactam antibiotic resistance, penicillin-binding protein 2A (encoded by the mecA gene), directly contributes to pathogenicity during MRSA infection. MecA induction leads to a reduction in peptidoglycan cross-linking that allows for enhanced degradation and detection by phagocytes, resulting in robust IL-1ß production. Peptidoglycan isolated from ß-lactam-challenged MRSA strongly induces the NLRP3 inflammasome in macrophages, but these effects are lost upon peptidoglycan solubilization. Mutant MRSA bacteria with naturally occurring reduced peptidoglycan cross-links induce high IL-1ß levels in vitro and cause increased pathology in vivo. ß-lactam treatment of MRSA skin infection exacerbates immunopathology, which is IL-1 dependent. Thus, antibiotic-induced expression of mecA during MRSA skin infection contributes to immunopathology by altering peptidoglycan structure.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Infecções Estafilocócicas
/
Proteínas de Bactérias
/
Peptidoglicano
/
Proteínas de Ligação às Penicilinas
/
Interleucina-1beta
/
Staphylococcus aureus Resistente à Meticilina
Limite:
Animals
Idioma:
En
Revista:
Cell Host Microbe
Ano de publicação:
2015
Tipo de documento:
Article