Bacitracin is a branched cyclic dodecylpeptide antibiotic produced by Bacillus licheniformis and some strains of Bacillus subtilis (Azevedo et al 1993). It is synthesized as a mixture of up to 50 closely related congeners/fractions. Bacitracin includes the following fractions: A, A1, B, B1, B2, B3, C, C1, C2, C3, D, E, F, G, H1, H2, H3, I1, I2, I3, and X. Bioactive components include A, B1, B2, and B3. Bacitracin is freely soluble in aqueous solution.
During the purification of Bacitracin, many peptide precursors are not removed and are detectable in finished commercial products. These peptides have an affinity for cell walls much like bioactive Bacitracin components. Liquid column chromatography is used to separate the impurities from the bioactive components. Each component has been collected and carefully tested for toxicity against routinely used cell lines. Only bioactive, non-toxic fractions are included in Bacitracin, CulturePure.
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| Mechanism of Action | Bacitracin prevents phosphorylation of bactoprenol, a transport protein which carries peptidoglycan components outside the cell membrane. Without the active phosphorylated bactoprenol, peptidoglycan synthesis cannot be completed and the cell lyses. Resistance to Bacitracin is understood to involve two mechanisms: A protein transporter (BcrABC) which pumps Bacitracin out of the cell after it has entered, and via another protein (BacA) which provides the active phosphorylated bactoprenol from a different synthetic pathway. |
| Spectrum | Bacitracin primarily targets the cell wall in members of the Gram-positive bacteria including Streptococcus pyogenes and Staphylococcus aureus. |
| Purity Level | Ultrapure, free of toxic and non-specific Bacitracin fractions |
| Microbiology Applications | Bacitracin is a useful tool to differentiate between ß-hemolytic, group A Streptococci (Streptococcus pyogenes) and ß-hemolytic Streptocococci of other groups. Bacitracin can be used as a supplement in chocolate agar to facilitate the isolation of Haemophilus influenzae. Bacitracin can be used to study the regulatory network in B. subtilis. By systematically analyzing the Bacitracin stimulon, authors can pinpoint the loci induced by Bacitracin (Mascher et al 2003). Bacitracin can be used for gene selection. bacA gene may confer resistance to Bacitracin in E. coli (Cain et al, 1993) |
| Plant Biology Applications | Tobacco hairy roots and cell suspensions were used in plant transformation studies to produce full length murine IgG1 monoclonal antibody. Bacitracin has been shown to prevent degradation of peptides and hormones in plant systems. Treatment with Bacitracin was not sufficient to prevent loss of antibody from the cultures, but improved the growth rates by up to 53% (Sharp and Doran, 1999). |
| Eukaryotic Cell Culture Applications | Bacitracin can be used for gene selection in cell culture applications. Bacitracin, CulturePure® (TOKU-E) was used to inhibit antithymocyte globulin (ATG)-mediated tissue factor (TF) activation and surface-associated, protein disulfide isomerase (PDI) activity in HL60 cells (Langer et al, 2013). Bacitracin, CulturePure (TOKU-E) was used as a PDI inhibitor to study its role in TF activation in cisplatin-treated NSCLC cells (Jacobsen et al, 2015) |
| Molecular Formula | C66H103N17O16S |
| Source | Bacillus subtilis and B. licheniformis |
| References | Bell, RG (1992) Preparative high-performance liquid chromatographic separation and isolation of Bacitracin components and their relationship to microbiological activity. J. Chromatog. 590:163-168 Cain BD, Norton PG, Eubanks W, Nick HS and Allen CM (1993) Amplification of the bacA gene confers bacitracin resistance to Escherichia coli. J. Bacteriol. 175(12):3784-3789 PMID 8389741 Jacobsen C et al (2015) Regulation of tissue factor in NT2 germ cell tumor cells by cisplatin chemotherapy. Thromb Res. 136(3):673-681 PMID 26205155 Langer F et al (2013) Rapid activation of monocyte tissue factor by antithymocyte globulin is dependent on complement and protein disulfide isomerase. Blood 121 (12):2324-2335 PMID 23315166 Mascher T, Margulis NG, Wang T, Ye RW, Helmann JD (2003) Cell wall stress responses in Bacillus subtilis: The regulatory network of the Bacitracin stimulon. Mol. Microbiol 50(5):1591-1604 PMID 14651641 Mueller MJ, Brodschelm W (1993) Signaling in the elicitation process is mediated through the octadecanoid pathway leading to jasmonic acid. Proc. Natl. Acad. Sci. 90: 7490-7494 PMID 11607420 Sharp, JM and Doran, PM (1999) Effect of Bacitracin on growth and monoclonal antibody production by tobacco hairy roots and cell suspensions. Biotechnol. Bioprocess Eng. 4: 253 Stone KJ and Strominger JL (1971) Mechanism of action of Bacitracin: Complexation with metal ion and C55-isoprenyl pyrophosphate. PNAS 68 (12): 3223-3227 PMID 4332017 Webb, NE (2015) Dose-response models reveal critical features of inhibitor activity and viral infection. phD dissertation. UCLA |
| MIC | Bacteroides fragilis (ATCC 25285)| >8 － ?| 650| Clostridium difficile| >256 － ?| 764| Clostridium perfringens (ATCC 13124)| 0.25 － ?| 650| Clostridium spiroforme (A7)| >8 － ?| 650| Clostridium spiroforme (A8)| >8 － ?| 650| Clostridium spiroforme (B61)| >8 － ?| 650| Clostridium spiroforme (BA 1)| >8 － ?| 650| Clostridium spiroforme (C121)| >8 － ?| 650| Clostridium spiroforme (CED 1)| >8 － ?| 650| Clostridium spiroforme (D11)| >8 － ?| 650| Clostridium spiroforme (D13)| 4 － ?| 650| Clostridium spiroforme (D14)| >8 － ?| 650| Clostridium spiroforme (NCTC 11493)| 8 － ?| 650| Clostridium spiroforme (RPO 980)| 8 － ?| 650| Diplococcus pneumoniae| 0.04 － 12.5| 1413| Enterococcus faecium| ≤1120 － ?| 837| Enterococcus faecium| ≤1120 － ?| 837| Escherichia coli| ≤560 － ?| 837| Escherichia coli| 800 － ?| 1541| Escherichia coli (14497)| 780 － ?| 1027| Escherichia coli (14497S)| 780 － ?| 1027| Escherichia coli (19568)| 780 － ?| 1027| Escherichia coli (19923)| 780 － ?| 1027| Escherichia coli (20384)| 780 － ?| 1027| Escherichia coli (20613)| 780 － ?| 1027| Escherichia coli (20619)| 780 － ?| 1027| Escherichia coli (3030-2)| 780 － ?| 1027| Escherichia coli (8829)| 780 － ?| 1027| Escherichia coli (8829S)| 780 － ?| 1027| Escherichia coli (ATCC 25922)| >8 － ?| 650| Escherichia coli (G58-1)| 1560 － ?| 1027| Escherichia coli (G58-1/pBR322)| 1560 － ?| 1027| Escherichia coli (JM109)| 390 － ?| 1027| Escherichia coli (JM109/pBR322)| 390 － ?| 1027| Fusarium oxysporum| 55 － ?| 1541| Fusobacterium necrophorum| 9.4 － 100| 1444| Haemophilus influenzae| >16 － ?| 120| Haemophilus influenzae| 50 － 400| 1413| Listeria innocua (7)| 50 － ?| 1024| Listeria monocytogenes (FBUNT)| 32 － ?| 1024| Listeria spp. (National Antimicrobial Resistance Monitoring Syste)| ≤8 － >128| 848| Neisseria gonorrhoeae| 800 － ?| 1541| Penicilium oxallicum| 50 － ?| 1541| Propionibacterium freudenreichii subsp. shermanii (131)| <1 － ?| 1029| Propionibacterium freudenreichii subsp. shermanii (NCIMB 10585)| <1 － ?| 1029| Propionibacterium freudenreichii subsp. shermanii (NCIMB 5959)| <1 － ?| 1029| Proteus vulgaris| 700 － ?| 1541| Pseudomonas aeruginosa| 700 － ?| 1541| Salmonella Agona (14749 + serovar B)| 3120 － ?| 1027| Salmonella Anatum (12453 + serovar E)| 3120 － ?| 1027| Salmonella Brandenburg (15865 + serovar B)| 3120 － ?| 1027| Salmonella Cerro (14294S + serovar D)| 1560 － ?| 1027| Salmonella Cerro (14824 + serovar D)| 1560 － ?| 1027| Salmonella Cerro (17390 + serovar D)| 1560 － ?| 1027| Salmonella Choleraesuis (12630 + serovar C1)| 3120 － ?| 1027| Salmonella Dublin (12133 + serovar D)| 3120 － ?| 1027| Salmonella Dublin (14178 + serovar D)| 1560 － ?| 1027| Salmonella Dublin (14178S + serovar D)| 1560 － ?| 1027| Salmonella Dublin (14294 + serovar D)| 1560 － ?| 1027| Salmonella Dublin (14347 + serovar D)| 1560 － ?| 1027| Salmonella Dublin (14534 + serovar D)| 1560 － ?| 1027| Salmonella Give (11520 + serovar E)| 3120 － ?| 1027| Salmonella Give (15065 + serovar E)| 3120 － ?| 1027| Salmonella Muenster (11814 + serovar E)| 3120 － ?| 1027| Salmonella Newport (12418 + serovar C2)| 3120 － ?| 1027| Salmonella Ohio (14497 + serovar C1)| 3120 － ?| 1027| Salmonella Stanley (17031 + serovar E)| 3120 － ?| 1027| Salmonella typhimurium| ≤1120 － ?| 837| Salmonella typhimurium (12948 + serovar B)| 3120 － ?| 1027| Staphylococcus aureus| 700 － ?| 1541| Staphylococcus aureus (8325)| 32 － ?| 806| Staphylococcus aureus (8325ΔpknB)| 32 － ?| 806| Staphylococcus aureus (ATCC 25923)| >8 － ?| 650| Staphylococcus aureus (ATCC 25923)| 16 － ?| 670| Staphylococcus aureus (erythromycin-resistant)| 2 － >4| 592| Staphylococcus aureus (erythromycin-susceptible + mupirocin-susceptible + oxacillin-susceptible)| ≤0.03 － >4| 592| Staphylococcus aureus (H14-KV)| 1 － ?| 670| Staphylococcus aureus (H5-KV)| 2 － ?| 670| Staphylococcus aureus (JSB20013)| 64 － ?| 748| Staphylococcus aureus (KSA)| 16 － ?| 670| Staphylococcus aureus (KVR)| 2 － ?| 670| Staphylococcus aureus (KVR-S)| 2 － ?| 670| Staphylococcus aureus (KVR-SR)| 8 － ?| 670| Staphylococcus aureus (KVR-Y)| 2 － ?| 670| Staphylococcus aureus (methicillin-resistant + mupirocin-resistant)| 2 － >16| 120| Staphylococcus aureus (methicillin-resistant)| 2 － >16| 120| Staphylococcus aureus (methicillin-susceptible)| 4 － >16| 120| Staphylococcus aureus (mupirocin-resistant)| 2 － >4| 592| Staphylococcus aureus (N315)| 16 － ?| 670| Staphylococcus aureus (N315ex)| 16 － ?| 670| Staphylococcus aureus (oxacillin-resistant)| 2 － >4| 592| Staphylococcus aureus (RN4220/tet(A)/pYH4)| 32 － ?| 748| Staphylococcus aureus (ΔIP)| 16 － ?| 670| Staphylococcus aureus (ΔIPH14)| 16 － ?| 670| Staphylococcus aureus (ΔIPH5)| 16 － ?| 670| Staphylococcus aureus (ΔIP-KV)| 2 － ?| 670| Staphylococcus auricularis (coagulase-negative + mupirocin-resistant)| 0.25 － >4| 592| Staphylococcus auricularis (coagulase-negative + mupirocin-susceptible + oxacillin-susceptible)| 4 － >4| 592| Staphylococcus auricularis (coagulase-negative + oxacillin-resistant)| 0.25 － >4| 592| Staphylococcus auricularis (LQC 5186)| 128 － ?| 836| Staphylococcus capitis (coagulase-negative + mupirocin-resistant)| 0.25 － >4| 592| Staphylococcus capitis (coagulase-negative + mupirocin-susceptible + oxacillin-susceptible)| 4 － >4| 592| Staphylococcus capitis (coagulase-negative + oxacillin-resistant)| 0.25 － >4| 592| Staphylococcus capitis (LQC 5184)| >128 － ?| 836| Staphylococcus caprae (LQC 5091)| 16 － ?| 836| Staphylococcus cohnii subsp. cohnii (LQC 5112)| 128 － ?| 836| Staphylococcus cohnii subsp. urealyticum (LQC 5195)| >128 － ?| 836| Staphylococcus epidermidis| 8 － >16| 120| Staphylococcus epidermidis (coagulase-negative + mupirocin-resistant)| 0.25 － >4| 592| Staphylococcus epidermidis (coagulase-negative + mupirocin-susceptible + oxacillin-susceptible)| 4 － >4| 592| Staphylococcus epidermidis (coagulase-negative + oxacillin-resistant)| 0.25 － >4| 592| Staphylococcus haemolyticus (coagulase-negative + mupirocin-resistant)| 0.25 － >4| 592| Staphylococcus haemolyticus (coagulase-negative + oxacillin-resistant)| 0.25 － >4| 592| Staphylococcus haemolyticus (LQC 5085)| >128 － ?| 836| Staphylococcus hominis (coagulase-negative + mupirocin-resistant)| 0.25 － >4| 592| Staphylococcus hominis (coagulase-negative + mupirocin-susceptible + oxacillin-susceptible)| 4 － >4| 592| Staphylococcus hominis (coagulase-negative + oxacillin-resistant）| 0.25 － >4| 592| Staphylococcus hominis (LQC 5012)| 16 － ?| 836| Staphylococcus intermedius (coagulase-negative + oxacillin-resistant)| 0.25 － >4| 592| Staphylococcus intermedius (LQC 5023)| 128 － ?| 836| Staphylococcus lugdunensis (coagulase-negative + mupirocin-susceptible + oxacillin-susceptible)| 4 － >4| 592| Staphylococcus lugdunensis (coagulase-negative + oxacillin-resistant)| 0.25 － >4| 592| Staphylococcus pyogenes (erythromycin-resistant)| 0.25 － >4| 592| Staphylococcus saprophyticus| 8 － >16| 120| Staphylococcus saprophyticus (coagulase-negative + mupirocin-resistant)| 0.25 － >4| 592| Staphylococcus saprophyticus (coagulase-negative + oxacillin-resistant)| 0.25 － >4| 592| Staphylococcus saprophyticus (LQC 5120)| >128 － ?| 836| Staphylococcus sciuri (LQC 5175)| 16 － ?| 836| Staphylococcus simulans (coagulase-negative + mupirocin-susceptible + oxacillin-susceptible)| 4 － >4| 592| Staphylococcus simulans (coagulase-negative + oxacillin-resistant)| 0.25 － >4| 592| Staphylococcus simulans (LQC 5187)| 128 － ?| 836| Staphylococcus warneri (coagulase-negative + mupirocin-resistant)| 0.25 － >4| 592| Staphylococcus warneri (coagulase-negative + mupirocin-susceptible + oxacillin-susceptible)| 4 － >4| 592| Staphylococcus warneri (coagulase-negative + oxacillin-resistant)| 0.25 － >4| 592| Staphylococcus warneri (LQC 5056)| >128 － ?| 836| Staphylococcus xylosus (LQC 5156)| >128 － ?| 836| Streptococci (Viridans group)| 2 － >16| 120| Streptococcus agalactiae| 2 － >16| 120| Streptococcus faecium| 850 － ?| 1541| Streptococcus pneumonia| 0.06 － >16| 120| Streptococcus pyogenes| 0.5 － >16| 120| Treponema hyodysenteriae| 12.5 － 50| 1427| |
