Study on interaction of vancomycin with bacterial cell wall peptidoglycan

Unfortunately, despite of work involved in understanding of the mechanism of bacterial virulence, especially Staphylococcus aureus, it has not been developed effective therapy against this bacteria. The first antibiotic used against this bacteria was penicillin, which was discovered by Alexander Fleming in 1928. A new generation of drugs introduced into therapy against Staphylococcus aureus and other Gram-positive bacteria are glycopeptide antibiotics. The most widespread and most commonly used are vancomycin and teicoplanin, discovered respectively in 1956 and 1978. As a result of frequent use of vancomycin VISA (ang. Vancomycin-intermediate Staphylococcus aureus) and VRSA (ang. Vancomycin-resistant Staphylococcus aureus) strains were discovered. The mechanism of action of this antibiotic based on the inhibition of the biosynthesis of bacterial cell wall peptidoglycan fragment. Forming stabilized by hydrogen bonds complex with terminal fragment of peptidoglycan (dipeptide d-Ala-d-Ala) vancomycin prevents its further crosslinking [2] (Fig. 1). However, in recent years other theories of the mechanism of action of glycopeptide antibiotics against Gram-positive bacteria were presented it seems to be crucial to find methods of selection of new antibiotics and for this purpose standard techniques of the analysis, including isothermal titration calorimetry (ITC) [3], nuclear magnetic resonance spectroscopy (NMR) [8–15], high performance liquid chromatography (HPLC) [16], capillary electrophoresis [17] or self-assembled monolayers (SAMs) [22] are used. Discovering new methods for studying of interaction between vancomycin and Gram-positive bacterial cell wall allows use it as a new technique for rapid selection of potential new antibiotics, including glycopeptide derivatives