The Combination of Membrane Disruption and FtsZ Targeting by a Chemotherapeutic Hydrogel Synergistically Combats Pathogens Infections

Author:

Wei Xianyuan1ORCID,Guo Jintong1,Geng Xiaorui1,Xue Bin12,Huang Shaohui34,Yuan Zhen1ORCID

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

Publisher

Wiley

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