Gramicidin

also known as: Gramicidin D, Gramicidin A, Gramicidin S

The first clinical antibiotic in history — a channel-forming peptide from soil bacteria discovered in 1939, still used today in topical triple-antibiotic ointments.

A 15-amino-acid linear peptide antibiotic from Bacillus brevis that forms ion channels in bacterial membranes, first used clinically in 1939 and still marketed as a topical antibiotic in Neosporin/Polysporin combinations.

Mechanism of action

Two molecules form a head-to-head beta-helical dimer spanning the bacterial membrane, creating a cation-selective channel (~4 angstrom) that collapses the membrane potential and proton motive force. The alternating L/D amino acid sequence creates a unique beta-helical structure. Effective primarily against Gram-positive bacteria.

Primary uses

Topical antibiotic (FDA-approved in combinations)
Ophthalmic preparations
Research: model ion channel for biophysics

Typical dosing

0.025 mg/mL (ophthalmic) 2-4 times daily (topical or ophthalmic only)

Never given systemically. Combined with bacitracin, polymyxin B, neomycin.

Regulatory status

FDA-approved topical antibiotic in combination products. First clinical use by Rene Dubos in 1939 — predating penicillin's clinical introduction.

References

[pubmed] Dubos RJ. "Studies on a bactericidal agent extracted from a soil bacillus." J Exp Med. 1939;70(1):1-10.
[review] Kelkar DA, Chattopadhyay A. "The gramicidin ion channel: a model membrane protein." Biochim Biophys Acta. 2007;1768(9):2011-2025.

Related peptides

Bacitracin

The topical first-aid antibiotic — one of the most widely used over-the-counter peptide antibiotics, found in virtually every household first-aid kit.

Polymyxin B

The gram-negative last resort — a cyclic lipopeptide antibiotic revived from the 1950s as a critical weapon against carbapenem-resistant Acinetobacter, Pseudomonas, and Klebsiella.

Daptomycin

A last-resort lipopeptide antibiotic — the first-in-class cyclic peptide that kills MRSA and VRE by depolarizing bacterial membranes, without resistance through traditional mechanisms.

Vancomycin

The iconic glycopeptide antibiotic — the gold-standard MRSA treatment for over 60 years, acting by binding D-Ala-D-Ala to block cell wall synthesis.

Disclaimer

This entry is for educational purposes only and does not constitute medical advice. Dosing information reflects published regulatory or research data and is not a recommendation. Many compounds described here are not approved for human use in the United States. Consult a licensed medical professional before considering any peptide therapy.