Bacterial membrane-induced disassembly of fluorescein aggregates enables selective imaging and killing of Gram-positive bacteria

Abstract

The escalating health threats posed by bacteria and the pressing issue of antibiotic resistance underscore the urgent need for selective detection technologies and antimicrobial reagents. Fluorescein's biocompatibility renders it the preferred fluorescent dye for in vivo imaging. This study reveals that compounds from the aliphatic chain-derived fluorescein series (BMP-alkyl) not only selectively stain and fluorescently image Gram-positive bacteria but also demonstrate the ability to rapidly eliminate them. The discovery of fluorescein's antibacterial properties is poised to have applications in antibiotic research due to its excellent biocompatibility. These amphiphilic BMP-alkyl compounds were easily synthesized through a one-step amidation process involving dicarboxyfluorescein and long-chain fatty amines. In aqueous solutions, the formed aggregates exhibited complete fluorescence quenching. Upon encountering the Gram-positive bacterial membrane, BMP-alkyl compounds underwent depolymerization, resulting in a single fluorescent molecule and the activation of fluorescence. Subsequently, as these amphiphilic fluoresceins continuously combined and entered the bacterial interior, the potential for bacterial membrane depolarization, membrane structure damage, and ultimately bacterial death ensued.