Bacitracin action

The biosynthesis of cell wall peptidoglycan, showing the sites of action of five antibiotics (shaded bars 1 = fosfomycin, 2 = cycloserine, 3 = bacitracin, 4 = vancomycin, 5 = 3-lactam antibiotics). Bactoprenol (BP) is the lipid membrane carrier that transports building blocks across the cytoplasmic membrane M, N-acetylmuramic acid Glc, glucose NAcGIc or G, /V-acetylglucosamine. 

The poly (ribitol phosphate) synthetase and poly (glycerol phosphate) synthetase are inhibited by vancomycin, novobiocin, and Crystal Violet. Other antibiotic substances which interfere with cell-wall synthesis (such as bacitracin, ristocetin, and streptomycin) are almost without effect on the isolated synthetases, and penicillin is inhibitory at high concentrations only. Moreover, penicillin, vancomycin, and bacitracin do not markedly inhibit synthesis of cell-wall glycosaminopeptide in vitro, although the synthetical activity of extracts of cells which have been pretreated with these antibiotics is lowered.Convincing evidence that the primary site of inhibition by antibiotics is the biosynthesis of cell-wall material has been obtained only for the penicillins and cycloserine, and it appears that the action of even those antibiotics may be more complex than was originally supposed. 

The second stage of cell wall synthesis. An ATP-requiring amidation of glutamic acid that occurs between steps 2 and 3 has been omitted. Points of action of the antibiotic inhibitors bacitracin and vancomycin are indicated. 

Most biologically active natural peptides are linear, but bacitracin is a leading member of the so-called cyclic peptide type of antibiotics. The commercial material, extracted from Bacillus subtilis, is a mixture of several compounds in which bacitracin A predominates. It exerts its action by inhibiting peptidoglycan synthesis and membrane function. Bacitracin has been a useful antibiotic since the 1960s, but its systemic use results in a number of toxic side effects, including nephrotoxicity. One cannot be sure which components of the mixture are responsible for the toxicity, and separation of natural constituents is complex and difficult. For this reason, an efficient synthesis of bacitracin A would be useful. 

Topical antibiotics with a narrow spectrum of action and low toxicity (eg, bacitracin and mupirocin) can be used for temporary control of bacterial growth and are generally preferred to antiseptics. Methenamine mandelate releases formaldehyde in a low antibacterial concentration at acid pH and can be an effective urinary antiseptic for long-term control of urinary tract infections. 

Inhibitors of ceil wall synthesis are suitable antibacterial agents because animal, including human, cells lack a cell wall. These agents exert a bactericidal action on growing or multiplying germs. Members of this class include p-lactam antibiotics such as the penicillins and cephalosporins, in addition to bacitracin and vancomycin. 

Miscellaneous Antibiotics. Because of the activity found in some of the materials in the early testing and that are discussed later under Bacitracin and Penicillin, a considerable number of antibiotics were screened with the hope that there would be a range of activity which might relate (a) to their antimicrobial activity, (b) to their mode of action as antibiotics, or (c) to some other biological relationship. The results of some of this work are shown in Table I (22). Our hopes were substantiated in that we have found a range of activity going from... 

Selective inhibition of bacterial cell wall synthesis (penicillins, cephalosporins, bacitracin, vancomycin). Following attachment to receptors (penicillinbinding proteins), p-lactam antibiotics inhibit transpeptidation enzymes and thereby block the final stage of peptidoglycan sysnthesis. This action is followed by inactivation of an inhibitor of autolytic enzymes in the bacterial cell wall. Bacitracin and vancomycin inhibit early stages of peptidoglycan synthesis. 

Derivation Action of zinc salts on bacitracin broth. 

The absorption-enhancing effects of protease inhibitors on the intestinal absorption of water-soluble compounds in rats was also examined. Some protease inhibitors may have absorption-enhancing activities in addition to their protease inhibitory actions (e.g., NaGC) [43, 44]. Aprotinin, bacitracin, and soybean trypsin inhibitor (STI) were used as protease inhibitors, while phenol red and fluorescein isothiocyanate (FITC)-labeled dextran with an average molecular weight of 4000 Da (FD-4) were selected as poorly absorbable and stable model compounds. Bacitracin enhanced the absorption of phenol red from the rat small and large intestine in the presence of the protease inhibitors, and similar results were noted for the intestinal absorption of FD-4 co-administered with bacitracin. Thus, bacitracin was seen to have not only a proteolytic inhibitory action but also an absorption-enhancing capability. 

Resistance to bacitracin does not emerge rapidly in originally susceptible strains. The thermal and storage stability of bacitracin is enhanced by the presence of an equimolar concentration of Zn " and the antibacterial action is potentiated by an excess of Zn " ". It has been suggested that Zn + is also associated with the mechanism of antibacterial action. No chemical assay methods are yet available for bacitracin. For the determination of potency the cylinder plate method with Micrococcus flavus (ATCC 10 240) as test organism is used. ... 

Zinc Bacitracin, fiacifracfn zinc complex bacitracin zinc salt Badferm. Contains about 7% Zn. Prepd by the action of zinc salts on bad trad n broth Anker et al, J. Bacterial S5, 249 (1948) Hodge, Lafferty as died in U.S. pat. 2,003,584 (1957 to CSC). The potency is usually between 50 and 60 units/mg of bacitracin activity Gross, Drug Coimet. Ind. 75, 612 (1954) Gross et al., J. Am. Pharm. Assoc., Sci. Ed. 45, 447 <1956). 

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