Affiliation:
1. Faculty of Health Sciences and Center for Cognitive and Brain Sciences University of Macau Macau SAR 999078 China
2. Shenzhen Key Laboratory of Ultraintense Laser and Advanced Material Technology Center for Intense Laser Application Technology and College of Engineering Physics Shenzhen Technology University Shenzhen 518118 China
3. School of Life Sciences University of Chinese Academy of Sciences Beijing 101499 China
4. LightEdge Technologies Limited Zhongshan Guangdong 528403 China
Abstract
AbstractThe 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.
Funder
Universidade de Macau
Fundo para o Desenvolvimento das Ciências e da Tecnologia
Natural Science Foundation of Guangdong Province