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The bacterial cytoplasmic membrane and cellular macromolecules represent a broad set of targets for antimicrobial agents, particularly biocides, antiseptics, and certain specialized antibiotics. The cytoplasmic membrane is a vital semi-permeable phospholipid bilayer responsible for energy transduction, nutrient transport, and maintaining the electrochemical gradient (Seltmann & Holst, 2002). Cellular macromolecules, including proteins, DNA, and RNA, serve as the functional and genetic machinery of the cell (McDonnell & Russell, 1999). Broad-spectrum agents like chlorhexidine and glutaraldehyde act by disrupting membrane integrity, denaturing proteins, or cross-linking nucleic acids, leading to rapid cell death (McDonnell & Russell, 1999). Some antibiotics, such as daptomycin, specifically target the membrane to cause depolarization and loss of membrane potential (Humphries et al., 2013). Because these targets are often conserved or lack high specificity, many agents acting on them are limited to topical or environmental use to avoid host toxicity (StatPearls, 2023). This multi-target approach is effective against a wide range of pathogens but presents challenges in terms of selectivity and systemic safety.
Disruption of membrane integrity, leakage of intracellular contents, denaturation of proteins, and chemical modification or cross-linking of cellular macromolecules such as DNA and RNA (McDonnell & Russell, 1999).
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