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The Gram-negative bacterial inner membrane and cytoplasmic contents represent the essential internal environment of the bacterium, encompassing the cytoplasmic membrane and the intracellular machinery required for life (Sohlenkamp & Geiger, 2016). The inner membrane is a phospholipid bilayer that serves as a selective permeability barrier and the site of the electron transport chain and ATP synthesis (Silhavy et al., 2010). Within the cytoplasm, the target includes the bacterial genome, 70S ribosomes, and various enzymes involved in metabolic pathways (Blair et al., 2015). Antibiotics such as polymyxins target the inner membrane to cause leakage of cytoplasmic contents, leading to cell death (Trimble et al., 2016). Other classes, including aminoglycosides and fluoroquinolones, must penetrate this membrane to reach their respective targets, the ribosome and DNA gyrase, to inhibit protein synthesis and DNA replication (Lewis, 2013). This broad categorization is typically viewed as a collection of multiple distinct therapeutic targets rather than a single molecular entity.
Disruption of the inner membrane phospholipid bilayer, inhibition of the 30S or 50S ribosomal subunits to block protein synthesis, and inhibition of DNA gyrase or topoisomerase IV to prevent DNA replication (Blair et al., 2015; Trimble et al., 2016).
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