Bacitracin is a polypeptide antibiotic. It is a mixture of related

cyclic peptides Cyclic peptides are polypeptide chains which contain a circular sequence of bonds. This can be through a connection between the amino and carboxyl ends of the peptide, for example in cyclosporin; a connection between the amino end and a side ch ...

produced by ''

Bacillus licheniformis ''Bacillus licheniformis'' is a bacterium commonly found in the soil. It is found on bird feathers, especially chest and back plumage, and most often in ground-dwelling birds (like sparrows) and aquatic species (like ducks). It is a gram-positi ...

'' bacteria, that was first isolated from the variety "Tracy I" ( ATCC 10716) in 1945. These peptides disrupt

Gram-positive bacteria In bacteriology, gram-positive bacteria are bacteria that give a positive result in the Gram stain test, which is traditionally used to quickly classify bacteria into two broad categories according to their type of cell wall. The Gram stain ...

by interfering with

cell wall A cell wall is a structural layer that surrounds some Cell type, cell types, found immediately outside the cell membrane. It can be tough, flexible, and sometimes rigid. Primarily, it provides the cell with structural support, shape, protection, ...

and peptidoglycan synthesis. Bacitracin is primarily used as a topical preparation, as it can cause kidney damage when used internally. It is generally safe when used topically, but in rare cases may cause

hypersensitivity Hypersensitivity (also called hypersensitivity reaction or intolerance) is an abnormal physiological condition in which there is an undesirable and adverse immune response to an antigen. It is an abnormality in the immune system that causes Imm ...

allergic Allergies, also known as allergic diseases, are various conditions caused by hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include hay fever, food allergies, atopic dermatitis, alle ...

anaphylactic Anaphylaxis (Greek: 'up' + 'guarding') is a serious, potentially fatal allergic reaction and medical emergency that is rapid in onset and requires immediate medical attention regardless of the use of emergency medication on site. It typically ...

reactions, especially in people allergic to

neomycin Neomycin, also known as framycetin, is an aminoglycoside antibiotic that displays bactericidal activity against Gram-negative aerobic bacilli and some anaerobic bacilli where resistance has not yet arisen. It is generally not effective against ...

. In 2022, it was the 323rd most commonly prescribed medication in the United States, with more than 100,000 prescriptions.

Medical uses

Bacitracin is used in human medicine as a polypeptide antibiotic and is "approved by the US

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...

(FDA) for use in chickens and turkeys," though use in animals contributes to

antibiotic resistance Antimicrobial resistance (AMR or AR) occurs when microbes evolve mechanisms that protect them from antimicrobials, which are drugs used to treat infections. This resistance affects all classes of microbes, including bacteria (antibiotic resis ...

. As bacitracin zinc salt, in combination with other topical antibiotics (usually

polymyxin B Polymyxin B, sold under the brand name Poly-Rx among others, is an antibiotic used to treat meningitis, pneumonia, sepsis, and urinary tract infections. While it is useful for many Gram negative infections, it is not useful for Gram positive infe ...

and

) as an

ointment A topical medication is a medication that is applied to a particular place on or in the body. Most often topical medication means application to body surfaces such as the skin or mucous membranes to treat ailments via a large range of classes ...

("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

infection An infection is the invasion of tissue (biology), tissues by pathogens, their multiplication, and the reaction of host (biology), host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmis ...

s. A non-ointment form of ophthalmic solution is also available for eye infections. 200px, 3D Chemical Structure of Bacitracin

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. * ''

Staphylococcus aureus ''Staphylococcus aureus'' is a Gram-positive spherically shaped bacterium, a member of the Bacillota, and is a usual member of the microbiota of the body, frequently found in the upper respiratory tract and on the skin. It is often posi ...

'' – ≤0.03 μg/mL – 700 μg/mL * ''

Staphylococcus epidermidis ''Staphylococcus epidermidis'' is a Gram-positive bacterium, and one of over 40 species belonging to the genus ''Staphylococcus''. It is part of the human flora, normal human microbiota, typically the skin flora, skin microbiota, and less commonl ...

'' – 0.25 μg/mL – >16 μg/mL * ''

Streptococcus pyogenes ''Streptococcus pyogenes'' is a species of Gram-positive, aerotolerant bacteria in the genus '' Streptococcus''. These bacteria are extracellular, and made up of non-motile and non-sporing cocci (round cells) that tend to link in chains. They ...

'' – 0.5 μg/mL – >16 μg/mL

Mechanism of action

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 Peptidoglycan or murein is a unique large macromolecule, a polysaccharide, consisting of sugars and amino acids that forms a mesh-like layer (sacculus) that surrounds the bacterial cytoplasmic membrane. The sugar component consists of alternating ...

bacterial

outside of the inner membrane.

History

Bacitracin was isolated by Balbina Johnson, a

bacteriologist A bacteriologist is a microbiologist, or similarly trained professional, in bacteriology— a subdivision of microbiology that studies bacteria, typically Pathogenic bacteria, pathogenic ones. Bacteriologists are interested in studying and learnin ...

at the

Columbia University College of Physicians and Surgeons The Columbia University College of Physicians and Surgeons (officially known as Columbia University Roy and Diana Vagelos College of Physicians and Surgeons) is the medical school of Columbia University, located at the Columbia University Irvin ...

. Its name derives from the fact that a compound produced by a microbe in young Margaret Tracy's (1936–1994) leg injury showed antibacterial activity.

''"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'."''

Bacitracin was approved by the US FDA in 1948.

Synthesis

Bacitracin is synthesised via

nonribosomal peptide synthetase Nonribosomal peptides (NRP) are a class of peptide secondary metabolites, usually produced by microorganisms like bacteria and fungi. Nonribosomal peptides are also found in higher organisms, such as nudibranchs, but are thought to be made by bacte ...

s (NRPSs), which means that

ribosome Ribosomes () are molecular machine, macromolecular machines, found within all cell (biology), cells, that perform Translation (biology), biological protein synthesis (messenger RNA translation). Ribosomes link amino acids together in the order s ...

s are not directly involved in its

synthesis Synthesis or synthesize may refer to: Science Chemistry and biochemistry *Chemical synthesis, the execution of chemical reactions to form a more complex molecule from chemical precursors **Organic synthesis, the chemical synthesis of organi ...

. The three-enzyme

operon In genetics, an operon is a functioning unit of DNA containing a cluster of genes under the control of a single promoter. The genes are transcribed together into an mRNA strand and either translated together in the cytoplasm, or undergo splic ...

is called BacABC, not to be confused with BacABCDE of bacilycin synthesis.

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. 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.

Society and culture

Controversies

Claims that bacitracin is a

protein disulfide isomerase Protein disulfide isomerase (), or PDI, is an enzyme in the endoplasmic reticulum (ER) in eukaryotes and the periplasm of bacteria that catalyzes the formation and breakage of disulfide bonds between cysteine residues within proteins as the ...

inhibitor are disputed by ''in vitro'' studies.

References

{{Authority control Polypeptide antibiotics Cyclic peptides