Total Structures and Antimicrobial Activity of Bacitracin Minor Components.

Abstract

Total structures of 13 minor components of bacitracin (BC) were proposed, and their antimicrobial activities were investigated. The components of BCincluding bacitracins A (BC-A) and F (BC-F) were isolated by preparative HPLCand were hydrolyzed under acidic conditions.The resulting amino acids were derivatized with l-fluoro-2,4-dinitrophenyl-5-L-alanineamide and were separated by HPLCto determine their absolute configurations. It was found that the TV-terminal amino acids of BC-Aand its related components were epimerized during the hydrolysis to yield their enantiomers. The formation of these artifactual amino acids suggests that our previously proposed structures of the BCminor componentsare incorrect; therefore, the structures were corrected based on these results. The structures of the BCminor componentswere the same as that of BCs-A and -F except that one to three of the L-isoleucines, including the TV-terminal one, were replaced by L-valines. These structures were confirmed by tandem mass spectrometry under fast atom bombardment (FAB) conditions and Frit-FAB liquid chromatography/mass spectrometry. Based on the UVspectra of the BC components determined by photodiode array detection-HPLC analysis, a new systematic nomenclature was proposed for the minor components. The isolated components were also used for the determination of their minimal inhibition concentrations and it was found that BC-Ais 2~8 times more potent than the other minor componentsagainst strains of Micrococcus luteus and Staphylocoecusaureus.

High-resolution crystal structure reveals molecular details of target recognition by bacitracin

“…S2). In contrast, we found that bacitracin's minimum inhibitory concentration (MIC) for this same strain is 0.5 mg/L, in good agreement with a previously reported value (11). Zinc alone showed no effect on membrane permeability, and the positive control, the known membrane-permeabilizing agent gramicidin S, caused immediate and rapid potassium efflux upon addition.…”

“…The peptides are cyclized into lariat structures via condensation of the e-amino group of a lysine side chain with the peptide C terminus (10). The most potent of the bacitracin congeners is bacitracin A, which contains a thiazoline ring at its N terminus, formed by the condensation of Ile-1 and Cys-2 (11,12) (Fig. 1).…”

The histopathological and ultrastructural effects of topical application of bacitracin on to the cerebral cortex in rats

“…Bacitracin is a peptide antibiotic produced by Bacillus subtilis and exhibits activity against Gram-positive organisms (22). Bacitracin is one of the most popular topical antibiotics used in the irrigation solution for neurosurgical cases (25,31,33,37).…”

Pathways of Chemical Degradation of Polypeptide Antibiotic Bacitracin

“…1,6,9,19,20) Other oxidative degradation products of microbiologically active components B1, B2 and B3 have almost not been mentioned, although Ikai and co-workers determined their molecular weights and proposed their structures and names H1, H2 and H3 respectively. 6) In our recently published HPLC method for Bc, the mentioned oxidative degradation products H1, H2 and H3 were chromatographically clearly defined for the first time. 21,22) We used mainly the new type monolithic silica reversed-phase Chromolith RP-18e (100ϫ4.6 mm I.D.)…”

“…1). 5,6,9,10) Recently the nomenclature for three minor components D1, D2 and D3 has been changed to C1, C2 and C3 respectively in the PharmEuropa 10) and in the Ph.Eur. 5 th .…”