Bacitracin Explained

Bacitracin[1] is a polypeptide antibiotic. It is a mixture of related cyclic peptides produced by Bacillus licheniformis bacteria, that was first isolated from the variety "Tracy I" (ATCC 10716) in 1945.[2] These peptides disrupt Gram-positive bacteria by interfering with cell wall and peptidoglycan synthesis.

Bacitracin is primarily used as a topical preparation, as it can cause kidney damage when used internally.[3] It is generally safe when used topically, but in rare cases may cause hypersensitivity, allergic or anaphylactic reactions, especially in people allergic to neomycin.[4] [5]

In 2021, it was the 300th most commonly prescribed medication in the United States, with more than 400,000 prescriptions.[6] [7]

Medical uses

Bacitracin is used in human medicine as a polypeptide antibiotic and is "approved by the US Food and Drug Administration (FDA) for use in chickens and turkeys," though use in animals contributes to antibiotic resistance.[8]

As bacitracin zinc salt, in combination with other topical antibiotics (usually polymyxin B and neomycin) as an ointment ("triple antibiotic ointment," with the brand name Neosporin), it is used for topical treatment of a variety of localized skin and eye infections, as well as for the prevention of wound infections. A non-ointment form of ophthalmic solution is also available for eye infections.[9]

Spectrum of activity and susceptibility data

Bacitracin is a narrow-spectrum antibiotic. It targets Gram-positive bacteria, especially those that cause skin infections. The following represents susceptibility data for a few medically significant microorganisms.[10]

Mechanism of action

See main article: Bactoprenol phosphate. Bacitracin interferes with the dephosphorylation of C55-isoprenyl pyrophosphate, and a related molecule known as bactoprenol pyrophosphate; both of these lipids function as membrane carrier molecules that transport the building-blocks of the peptidoglycan bacterial cell wall outside of the inner membrane.[11]

History

Bacitracin was isolated by Balbina Johnson, a bacteriologist at the Columbia University College of Physicians and Surgeons. Its name derives from the fact that a compound produced by a microbe in young Margaret Tracy's (1936–1994)[12] leg injury showed antibacterial activity.[13]

One strain isolated from tissue debrided from a compound fracture of the tibia was particularly active. We named this growth-antagonistic strain for the patient, "Tracy I." When cell-free filtrates of broth cultures of this bacillus proved to possess strong antibiotic activity and to be non-toxic, further study seemed warranted. We have called this active principle "Bacitracin.[14]

Bacitracin was approved by the US FDA in 1948.[15]

Synthesis

Bacitracin is synthesised via nonribosomal peptide synthetases (NRPSs), which means that ribosomes are not directly involved in its synthesis. The three-enzyme operon is called BacABC, not to be confused with BacABCDE of bacilycin synthesis.[16]

Composition

Bacitracin is composed of a mixture of related compounds with varying degrees of antibacterial activity. Notable fractions include bacitracin A, A1, B, B1, B2, C, D, E, F, G, and X.[17] Bacitracin A has been found to have the most antibacterial activity. Bacitracin B1 and B2 have similar potencies and are approximately 90% as active as bacitracin A.[18]

Society and culture

Controversies

Claims that bacitracin is a protein disulfide isomerase inhibitor are disputed by in vitro studies.[19] [20]

Notes and References

  1. Book: Elks J, Ganellin CR . The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. 1990. Springer. 978-1-4757-2085-3. 119–.
  2. Originally grouped under B. subtilis, but nomenclature has since changed. See Web site: Podstawka A . Bacillus licheniformis Tracy I DSM 603, ATCC 10716, CCM 2181, IFO 12199, NBRC 12199, NCIB 8874, FDA BT1 BacDiveID:686 . bacdive.dsmz.de . en . 7 February 2022 . 7 February 2022 . https://web.archive.org/web/20220207144504/https://bacdive.dsmz.de/strain/686 . live .
  3. Zintel HA, Ma RA . The absorption, distribution, excretion and toxicity of bacitracin in man . The American Journal of the Medical Sciences . 218 . 4 . 439–445 . October 1949 . 18140540 . 10.1097/00000441-194910000-00012 . 2371497 .
  4. Spann CT, Taylor SC, Weinberg JM . Topical antimicrobial agents in dermatology . Disease-a-Month . 50 . 7 . 407–421 . July 2004 . 15280871 . 10.1016/j.disamonth.2004.05.011 .
  5. Trookman NS, Rizer RL, Weber T . Treatment of minor wounds from dermatologic procedures: a comparison of three topical wound care ointments using a laser wound model . Journal of the American Academy of Dermatology . 64 . 3 Suppl . S8-15 . March 2011 . 21247665 . 10.1016/j.jaad.2010.11.011 . free .
  6. Web site: The Top 300 of 2021 . ClinCalc . 14 January 2024 . 15 January 2024 . https://web.archive.org/web/20240115223848/https://clincalc.com/DrugStats/Top300Drugs.aspx . live .
  7. Web site: Bacitracin - Drug Usage Statistics . ClinCalc . 14 January 2024.
  8. Web site: Pearl MC . 12 September 2007 . Antibiotic use on the farm hurts people—and doesn't help the bottom line. . . https://web.archive.org/web/20070925063617/http://discovermagazine.com/2007/sep/better-planet . 25 September 2007 .
  9. Web site: Healthgrades > Find a Doctor > Doctor Reviews > Hospital Ratings. dead. https://web.archive.org/web/20110523141000/http://www.healthgrades.com/drug-ratings/drug/information/1246/Triple%20Antibiotic. 23 May 2011.
  10. Web site: Bacitracin Susceptibility and Minimum Inhibitory Concentration (MIC) Data . TOKU-E . 12 August 2013 . 22 December 2018 . https://web.archive.org/web/20181222141944/http://www.toku-e.com/Assets/MIC/Bacitracin.pdf . live .
  11. Stone KJ, Strominger JL . Mechanism of action of bacitracin: complexation with metal ion and C 55 -isoprenyl pyrophosphate . Proceedings of the National Academy of Sciences of the United States of America . 68 . 12 . 3223–7 . December 1971 . 4332017 . 389626 . 10.1073/pnas.68.12.3223 . 1971PNAS...68.3223S . free . doi .
  12. Web site: Margaret Tracy & Balbina Johnson: The Women Behind Bacitracin . 30 September 2014 . dead . https://web.archive.org/web/20140428190211/https://files.nyu.edu/jmm257/public/other/bacitracin.html . 28 April 2014 .
  13. Web site: NewYork-Presbyterian | the Discovery of Bacitracin. 7 February 2017. 9 April 2020. 27 February 2021. https://web.archive.org/web/20210227164020/https://healthmatters.nyp.org/bacitracin-discovery/. live.
  14. Johnson BA, Anker H, Meleney FL . Bacitracin: a new antibiotic produced by a member of the B. subtilis group . Science . 102 . 2650 . 376–7 . October 1945 . 17770204 . 10.1126/science.102.2650.376 . 1945Sci...102..376J . 51066 .
  15. Web site: Drugs@FDA: FDA-Approved Drugs. 17 September 2021. U.S. Food and Drug Administration (FDA). 27 July 2021. https://web.archive.org/web/20210727171910/https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=060733. dead.
  16. Konz D, Klens A, Schörgendorfer K, Marahiel MA . The bacitracin biosynthesis operon of Bacillus licheniformis ATCC 10716: molecular characterization of three multi-modular peptide synthetases . Chemistry & Biology . 4 . 12 . 927–937 . December 1997 . 9427658 . 10.1016/s1074-5521(97)90301-x . doi . free .
  17. "Committee for Veterinary Medicinal Products Bacitracin." Ema.europa.eu. The European Agency for the Evaluation of Medicinal Products, June 1998. Web. 18 January 2013
  18. Bell RG . Preparative high-performance liquid chromatographic separation and isolation of bacitracin components and their relationship to microbiological activity . Journal of Chromatography . 590 . 1 . 163–8 . January 1992 . 1601975 . 10.1016/0021-9673(92)87018-4 . free .
  19. Karala AR, Ruddock LW . Bacitracin is not a specific inhibitor of protein disulfide isomerase . The FEBS Journal . 277 . 11 . 2454–62 . June 2010 . 20477872 . 10.1111/j.1742-4658.2010.07660.x . 37519169 .
  20. Weston BS, Wahab NA, Roberts T, Mason RM . Bacitracin inhibits fibronectin matrix assembly by mesangial cells in high glucose . Kidney International . 60 . 5 . 1756–64 . November 2001 . 11703593 . 10.1046/j.1523-1755.2001.00991.x . free . doi .

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