The Combination of Membrane Disruption and FtsZ Targeting by a Chemotherapeutic Hydrogel Synergistically Combats Pathogens Infections.
Adv Healthc Mater
; 13(19): e2304600, 2024 Jul.
Article
em En
| MEDLINE
| ID: mdl-38491859
ABSTRACT
The emergence of multidrug-resistant (MDR) bacteria poses a significant challenge to global health. Due to a shortage of antibiotics, alternative therapeutic strategies are urgently needed. Unfortunately, colistin, the last-resort antibiotic, has unavoidable nephrotoxicity and hepatotoxicity, and its single killing mechanism is prone to drug resistance. To address this challenge, a promising combinatorial approach that includes colistin, a membrane-disrupting antimicrobial agent, and chelerythrine (CHE), a FtsZ protein inhibitor is proposed. This approach significantly reduces antibiotic dose and development of resistance, leading to almost complete inactivation of MDR pathogens in vitro. To address solubility issues and ensure transport, the antimicrobial hydrogel system LNP-CHE-CST@hydrogel, which induced reactive oxygen species (ROS) and apoptosis-like cell death by targeting the FtsZ protein, is used. In an in vivo mouse skin infection model, the combination therapy effectively eliminated MDR bacteria within 24 h, as monitored by fluorescence tracking. The findings demonstrate a promising approach for developing multifunctional hydrogels to combat MDR bacterial infections.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas de Bactérias
/
Hidrogéis
/
Proteínas do Citoesqueleto
/
Antibacterianos
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article