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Microbial membrane and DNA represent two of the most critical structural and functional targets in antimicrobial therapy, encompassing the physical integrity and the genetic blueprint of pathogens [1]. The microbial membrane, whether the peptidoglycan-associated bacterial envelope or the ergosterol-containing fungal membrane, serves as a selective barrier and a platform for bioenergetics; its disruption by agents such as polymyxins or daptomycin leads to rapid depolarization and cell death [2][5]. Simultaneously, microbial DNA is the essential template for replication and transcription, making it a high-value target for bactericidal agents [3]. Fluoroquinolones exert their effect by inhibiting DNA gyrase and topoisomerase IV, preventing the resolution of DNA supercoiling during replication, while nitroimidazoles like metronidazole cause direct oxidative cleavage of the DNA backbone [4]. While these targets offer broad-spectrum potential, therapeutic challenges include significant systemic toxicities—such as nephrotoxicity with membrane-disrupting agents—and the pervasive threat of multi-drug resistance (MDR) [6]. Understanding the interplay between these targets is vital for developing next-generation anti-infectives that can bypass existing resistance mechanisms [3][6].
Disruption of membrane integrity, pore formation, and depolarization; inhibition of DNA replication, induction of DNA strand breaks, and inhibition of topoisomerases.
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