The Bacitracin Complex

Bacitracin is a commonly used topical antibiotic produced by certain strains of Bacillus licheniformis and Bacillus subtilis. [1] It is effectively used against gram-positive bacteria like cocci and bacilli, interfering with bacterial cell wall synthesis and the receptors involved in peptidoglycan synthesis. [2] Bacitracin is not administered systemically as it is nephrotoxic. [3] Despite its use in everyday human and veterinary medicine, bacterial resistance to bacitracin is still scarce. Resistance to peptide antibiotics occurs rarely compared to other antibiotics. [1]

Bacitracin is a complex, containing several polypeptide congeners. While numerous fractions like A, B1, B2, B3, C, D, H1, H2, H3, Xa and Xa1 have been described, 96% of the total antimicrobial activity in commercial products is made up of bacitracin A, bacitracin B1, bacitracin B2 and bacitracin B3; all others can be considered minor components. Many of the minor components, like the H, F and X congeners, are degradation products. [1]

As a peptide antibiotic, bacitracin has a characteristic cyclic peptide structure with a hydrophobic side chain. Below is Figure 1 from “Pathways of Chemical Degradation of Polypeptide Antibiotic Bacitracin” [1] showing the comparative structure of a few bacitracin components:

The potency of the bacitracin congeners varies wildly. Ikai et al tested nine congeners on their gram-positive antibacterial activity. They found that bacitracin A was 2-4 times more potent than the commercial bacitracin complex. Bacitracin B1, bacitracin B2 and bacitracin B3 all showed potencies similar to the commercial bacitracin, while bacitracin D1, bacitracin D2 and bacitracin D3 showed half the potency of commercial bacitracin. Although bacitracin F is a degradation product of the most potent congener, bacitracin A, it shows no bioactivity at all. [4]

Twelve years later, Pavli and Kmetec found the same by comparing the activity of bacitrains B1, B2, B3 and A to their respective oxidative degradation products H1, H2, H3 and F. They also compared the desamido degradation products of bacitracin A, bacitracins Xa and Xa1. Again, the degradation products showed very low bioactivity.

There is little recent research on the toxicity of the individual bacitracin components, and Pavli and Kmetec suggest that “it would be useful to check the credibility of the old and frequently quoted information about nephrotoxicity of the component F if [bacitracin] is used parenterally.”

Understanding the individual congeners, their structures and how they degrade and lose effectiveness can help us store and utilize bacitracin to its fullest potential. Could protecting from and filtering out degradation products could lead to a more effective clinical antimicrobial? TOKU-E looks forward to reading more about the different efficacies and toxicities of bacitracin’s components.


[1] Pavli, V., & Kmetec, V. (2006). Pathways of chemical degradation of Polypeptide antibiotic Bacitracin. Biological & Pharmaceutical Bulletin, 29(11), 2160–2167.

[2] Suleiman, S. A., Song, F., Su, M., Hang, T., & Song, M. (2016). Analysis of bacitracin and its related substances by liquid chromatography tandem mass spectrometry. Journal of Pharmaceutical Analysis.

[3] Ming, L.-J., & Epperson, J. D. (2002). Metal binding and structure–activity relationship of the metalloantibiotic peptide bacitracin. Journal of Inorganic Biochemistry, 91(1), 46–58.

[4] Ikai, Y., Oka, H., Hayakawa, J., Matsumoto, M., Saito, M., Harada, K.-I., … Suzuki, M. (1995). Total structures and Antimicrobial activity of Bacitracin minor components. The Journal of Antibiotics, 48(3), 233–242.