Gramicidins

Gramicidins are a family of antimicrobial peptides produced by the soil bacterium Bacillus brevis. They are linear pentadecapeptides that act by forming transmembrane channels in lipid bilayers. The gramicidin preparation is a mixture of several related compounds, principally gramicidins A, B, and C, with gramicidin A usually the most abundant and most active.

The mechanism of action involves two gramicidin molecules aligning head-to-head to form a dimeric channel that spans the membrane. The resulting pore is permeable to monovalent cations such as Na+, K+, and H+, dissipating the proton motive force and leading to cell death. The hydrophobic nature of gramicidins allows deep insertion into membranes, which explains both their antimicrobial activity and their mammalian cell toxicity.

In terms of spectrum and use, gramicidins are most active against Gram-positive bacteria; Gram-negative bacteria are relatively resistant due to their outer membrane barrier. Because of toxicity to human cells, gramicidins are typically used only topically (and in some ophthalmic formulations) and are not employed for systemic therapy. They are often formulated in combination with other topical antibiotics to broaden coverage and reduce resistance.

History and chemistry notes: Gramicidins were discovered in 1939 by René Dubos from Bacillus brevis. They are short, linear peptides with 15 amino acids and alternating D- and L- configurations, which contributes to their distinctive membrane-perturbing properties. Today, their clinical use is largely limited to topical applications due to safety concerns with systemic administration.