Gramicidin

Gramicidin (gramicidin D) is a mixture of linear 15-amino acid antimicrobial peptides produced by Bacillus brevis, comprising gramicidin A (~80%), B (~5%), and C (~15%). It is used topically as an antibiotic and is a component of Neosporin Ophthalmic Solution. Gramicidin acts by forming ion-conducting channels in bacterial cell membranes. Gramicidin S is a structurally distinct cyclic variant.

Gramicidin A, B, and C form head-to-head dimers that insert into lipid bilayers as single-stranded beta-helices, creating cation-selective transmembrane pores approximately 4 Å in diameter. These channels allow free diffusion of monovalent cations (Na+, K+, H+) but exclude divalent cations and anions. Disruption of the bacterial membrane ion gradient collapses the electrochemical potential, inhibiting ATP synthesis and nutrient transport, ultimately causing cell death. Channel formation is particularly effective in gram-positive bacterial membranes. Gramicidin is too cytotoxic for systemic use due to erythrocyte lysis.

Gramicidin has been used topically since the 1940s and remains in Neosporin Ophthalmic (gramicidin 0.025 mg/mL + neomycin + polymyxin B). It is among the first antibiotics to have its ion channel mechanism elucidated and serves as a canonical model system in biophysics research. Gramicidin's channel properties are studied with single-channel electrophysiology and have informed the design of synthetic ion channel-forming peptides. Gramicidin S (cyclic) is studied for broader antibacterial applications including MRSA, with ongoing analog development.