Polymyxin Family

Polymyxin Family (Polymyxin, Aerosporin, Circidin, Polypeptin) 

The discovery of antibiotic substances secreted by various strains of Bacillus polymyxa was simultaneously made in 1947 by Benedict and Langlykke (58) and by Stansly, Shepherd, and White (545). The latter workers, in particular, described the production and purification of a biologically active substance, which they named polymyxin. At almost the same time, Ainsworth, Brown, and Brownlee (16) announced the discovery of the production of a new antibiotic called aerosporin, by B. aerosporus, a species closely related to B. polymyxa. Later aerosporin was classified with the polymyxin group under the name polymyxin A. Actually, it appears that there are several polymyxins, each synthesized by different strains of B. polymyxa (326,327). A given strain, in general, synthesizes only one polymyxin (327). 

The polymyxins are antibiotic, basic, heteromeric peptides, which are active only against Gram-negative bacteria. They all contain L-a,Y-diaminobutyric acid, L-threonine, and (4-)6-methyloctanoic acid (55,114, 

Table IX (326,541) summarizes the amino acid composition of the various polymyxins. 

Polymyxins. butyric acid nine octanoic acid cine alanine  

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Colistin is a linear-ring peptide antibiotic. Its main components are colistin A and colistin B. It is a member of the polymyxin family of antibiotics that is stable in dry form and in water solution. The sulfate salt of colistin, which is usually administered as feed additive, is soluble in water, slightly soluble in methanol, and practically insoluble in acetone and ether. Colistin components do not have any specific fluorophore and UV chromophore, so detection by liquid chromatography at residue levels of interest is difficult without including a suitable derivatization step in the analytical method. 

There are relatively few chemotherapeutic drugs which cause permeability increases in membranes such as the antifungal polyenes and the antibacterial circular oligopeptides of the tyrocidin, gramicidin and polymyxin families. Most of these are too toxic for systemic use but polymyxins have been given systemically in severe Pseudomonas infections with an attending risk of renal toxicity. 

Polymyxins. Polymyxin B [1404-26-8] and polymyxin E [1066-17-7] (colistin) are the only medically important antibacterials from a group of some thirty closely related cyclic decapeptide antibiotics in the polymyxin family, some of which are given in Table 2. Most family members contain a seven amino acid ring attached to a three amino acid tail, to which is attached a fatty acyl group. The octapeptins have a tail containing a single amino acid. Each antibiotic contains several L-a-y-diaminobutyric acid [1758-80-1], C4H10N2O2, (Dab) residues, L-threonine [72-19-5], at least one D-amino acid, and one of a very limited list of fatty acids. 

Among the members of the polymyxin family the structures of polymyxin Bj, polymyxin Bj, colistin A (polymyxin Ej), colistin B (polymyxin E ) and... 

Microorganisms. For example, bacitracin and polymyxin are obtained from some Bacillus species streptomycin, tetracyclines, etc. from Streptomyces species gentamicin from Mi-cromonospora purpurea griseofulvin and some penicillins and cephalosporins from certain genera (Penicillium, Acremonium) of the family Aspergillaceae and monobactams from Pseudomonas acidophila and Gluconobacter species. Most antibiotics in current use have been produced from Streptomyces spp. 

The polypeptides include bacitracin A, colistin (polymyxin E), novobiocin, and polymyxin B. Bacitracin is a complex mixture of branched, cyclic decapeptides produced by Bacillus subtilise, which was first isolated in 1945. The polymyxins, discovered in 1947, are synthesized by various strains of Bacillus polymyxa. Colistin (polymyxin E) comprises a family of polymyxins and was known as colimycin when first isolated from a broth of Bacillus polymyxa var. colistinus in 1951. The polymyxins are cationic detergents. Novobiocin, first reported in 1955 as streptonivicin, is produced by the actinomycete Streptomyces niveus. 

Phytophthora megasperma, an often used elicitor, and chitosan were not active on these cultures. On the other hand, polypeptide antibiotics, like polymyxin B, were found to be the most active elicitors. The yeast extract elicitor was tested on callus cultures of 190 different plant species from 25 families. The strongest effects were found in seven species and subspecies of Eschscholtzia, Chelidonium majus, Glaucium rubrum, G. flava, Cory-dalis ophiocarpa, and Papaver somniferum, and in all cases the production of the quaternary phenanthridine alkaloids was induced, as easily recognized by the red coloration of the cultures. 

A strain of Bacillus circulans was found to produce a family of basic water-soluble lipopeptides designated as octapeptins which exhibited antibiotic activity against Gram negative bacteria. These lipopeptides show similarities to the polymyxins which are not discussed here because of the insufficient length of their acyl chain. All these lipopeptides have a high content of 2,4-diaminobutyric acid (DAB), five DAB residues out of eight amino acids in the case of the octapeptins. 

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