Ever since the discovery of antibiotics in the 1920’s, treating bacterial infections in humans, and animals alike, has emerged as a revolutionary possibility. Antibiotics are drugs that are naturally produced by bacteria or fungus to defend against other bacteria via death or inhibiting reproduction (1). Since their detection, antibiotics have been diversified into many different forms and classes which are arranged by mode of action. Glycopeptides are a class of antibiotics which are composed of glycolsylated cyclic or polycyclic nonribosomal peptides that inhibit cell wall synthesis in susceptible bacteria (2). However, it was soon discovered that the use of these antibiotic drugs would lead to antibiotic resistance. This paper will discuss the history, function, and resistance associated with vancomycin, a glycopeptide antibiotic.
Vancomycin, which is a specific antibiotic that falls under the glycopeptide subset of antibiotics was first discovered from a soil sample in the Bornea jungle by Dr. E. C. Kornfield during an antimicrobial research program in 1953 (2). Vancomycin is a bactericide collected from a strain of bacteria known as Streptomyces orientalis, and upon its initial mass production in the 1950s, was found to have many impurities which may have led to its early ototoxic and nephrotoxic properties making it a secondary drug upon initial approval by the FDA (3). However, it has since been more highly purified, and those properties have dissipated leaving a very pure, low toxicity antimicrobial agent. It is now used a last resort antibiotic and most prominently administered intravenously; however, studies are taking place to interpret the best way to administer the drug as new Vancomycin-resistant species have been identified (8).
Functions/ Mode of Action
This glycopeptide antibiotic works by inhibiting cell wall synthesis in susceptible bacteria, thus preventing the addition of new peptidoglycan inserts, ultimately causing cell death.
Specific Target of Glycopeptide Antibiotics
The action of glycopeptide antibiotics is to prevent the incorporation of N-acetylmuramic acid (NAM)- and N-acetylglucosamine (NAG)-peptide subunits from being incorporated into the peptidoglycan matrix of bacteria cell walls by the enzyme glycosyltransferease (4). The structure of Vancomycin contains a cleft into which highly specific amino acid chains, only found gram positive bacterial cell walls, can fit (5). When the substance binds to the ends of these D-Ala-D-Ala subunits on the NAM/NAG-peptide, it inhibits hydrogen bonding between the peptidoglycan precursors, thus preventing new peptidoglycan walls from forming (4). When the cell wall synthesis is prohibited by this large molecule, the rigidity and structure is altered causing cell wall permeability and alignment problems leading to cell apoptosis, or death.
Peptidoglycan’s Function in Bacteria
Peptidoglycan subunits are the building blocks for cell wall synthesis in gram positive...