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The Amphotericin B–colistin molecular complex is a synergistic association of two potent antimicrobial agents: the polyene antifungal amphotericin B and the polymyxin antibiotic colistin [1, 2]. It is not a biological target, such as a receptor or enzyme, but rather a drug-drug interaction or formulation used to combat multi-drug resistant (MDR) pathogens [1]. Amphotericin B functions by binding to ergosterol in fungal cell membranes, causing lethal pore formation, while colistin disrupts the outer membrane of Gram-negative bacteria and enhances the uptake of other drugs in fungal cells [3, 4]. Studies using molecular dynamics simulations have shown that these two molecules can self-assemble into a stable complex in aqueous media through hydrogen bonding and hydrophobic interactions [2]. This combination is primarily investigated for its efficacy against recalcitrant fungal infections, including those caused by Candida auris and Mucorales species, where monotherapy often fails [1, 5]. However, the clinical application of this complex is significantly challenged by the high risk of additive nephrotoxicity, requiring careful monitoring of renal function [4]. The complex represents a strategy of drug repurposing to expand the therapeutic window against emerging infectious threats [1].
The complex exerts synergistic antimicrobial effects by simultaneously targeting different components of the microbial cell membrane. Amphotericin B binds to ergosterol, creating ion-leaking pores, while colistin (polymyxin E) acts as a surfactant that disrupts the lipid bilayer and increases the permeability of the membrane to other agents [1, 4, 5].
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