On-demand recession of quaternary ammonium biocides for combating multidrug resistance.

Han, Wenwen; Cheng, Xin; Luo, Yimeng; Ma, Antong; Xu, Xiao-Qi; Du, Wenbin; Wang, Yapei · Biomaterials · 2026

basic_science · Level V

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Abstract

Antibiotic misuse is a key driver of antimicrobial resistance, but extensive use and prolonged environmental persistance of disinfectants like quaternary ammonium compounds (QACs), poses an urgent and underappreciated threat. Conventional QACs accumulate at sub-inhibitory concentrations (sub-MICs), accelerating multidrug resistance (MDR) in bacteria via sustained selection pressure. We introduce R-substituted silaketal-bridged QACs (RSBQs), which feature acid-cleavable linkages that enable controllable hydrolysis from bactericidal to non-toxic states. By modulating the R-substituents and environmental conditions, degradation half-lives range from 12 h to 6 days, reducing selection pressure before resistance establishes. Even at sub-MICs, partially degraded RSBQs such as ethyl-substituted SBQ (Et-SBQ) and n-propyl-substituted SBQ (nPr-SBQ), exhibit dual resistance-suppression, including downregulation of resistance gene expression and inhibition of efflux pump activity. By resensitizing multidrug-resistant bacteria to antibiotics, Et-SBQ synergized with ciprofloxacin to accelerate wound healing in mice. This strategy combines potent antibacterial activity, environmental degradability, and resistance suppression, offering a promising MDR solution.