Membrane Microdomain Disassembly Inhibits MRSA Antibiotic Resistance.
Cell
; 171(6): 1354-1367.e20, 2017 Nov 30.
Article
em En
| MEDLINE
| ID: mdl-29103614
ABSTRACT
A number of bacterial cell processes are confined functional membrane microdomains (FMMs), structurally and functionally similar to lipid rafts of eukaryotic cells. How bacteria organize these intricate platforms and what their biological significance is remain important questions. Using the pathogen methicillin-resistant Staphylococcus aureus (MRSA), we show here that membrane-carotenoid interaction with the scaffold protein flotillin leads to FMM formation, which can be visualized using super-resolution array tomography. These membrane platforms accumulate multimeric protein complexes, for which flotillin facilitates efficient oligomerization. One of these proteins is PBP2a, responsible for penicillin resistance in MRSA. Flotillin mutants are defective in PBP2a oligomerization. Perturbation of FMM assembly using available drugs interferes with PBP2a oligomerization and disables MRSA penicillin resistance in vitro and in vivo, resulting in MRSA infections that are susceptible to penicillin treatment. Our study demonstrates that bacteria possess sophisticated cell organization programs and defines alternative therapies to fight multidrug-resistant pathogens using conventional antibiotics.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Infecções Estafilocócicas
/
Microdomínios da Membrana
/
Staphylococcus aureus Resistente à Meticilina
Limite:
Animals
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article