Reducing Peptidoglycan Crosslinking by Chemical Modulator Reverts ß-lactam Resistance in Methicillin-Resistant Staphylococcus aureus.
Adv Sci (Weinh)
; 11(28): e2400858, 2024 Jul.
Article
em En
| MEDLINE
| ID: mdl-38747156
ABSTRACT
Small molecule can be utilized to restore the effectiveness of existing major classes of antibiotics against antibiotic-resistant bacteria. In this study, it is demonstrated that celastrol, a natural compound, can modify the bacterial cell wall and subsequently render bacteria more suceptible to ß-lactam antibiotics. It is shown that celastrol leads to incomplete cell wall crosslinking by modulating levels of c-di-AMP, a secondary messenger, in methicillin-resistant Staphylococcus aureus (MRSA). This mechanism enables celastrol to act as a potentiator, effectively rendering MRSA susceptible to a range of penicillins and cephalosporins. Restoration of in vivo susceptibility of MRSA to methicillin is also demonstrated using a sepsis animal model by co-administering methicillin along with celastrol at a much lower amount than that of methicillin. The results suggest a novel approach for developing potentiators for major classes of antibiotics by exploring molecules that re-program metabolic pathways to reverse ß-lactam-resistant strains to susceptible strains.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Peptidoglicano
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Resistência beta-Lactâmica
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Staphylococcus aureus Resistente à Meticilina
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Antibacterianos
Limite:
Animals
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article