Like many antibiotics (including the penicillins), vancomycin acts by interfering with the construction of cell walls in bacteria. Cell wall biosynthesis is one of the major means of killing bacteria.
The Bacterial Cell Wall. Bacterial cells are surrounded by a cell wall that is composed of a mesh-like network called peptidoglycan. The cell wall is absolutely crucial to the survival of the bacterium, for it provides the entire cell with mechanical support. The cell faces a huge intracellular osmotic pressure, and the rigidity of the peptidoglycan helps to maintain the cell’s shape and prevent it from lysing (exploding). Inhibition of the biosynthetic pathway of the peptidoglycan layer in bacteria will therefore cause the cell to lyse.
The peptidoglycan layer is composed of a linear polysaccharide chain composed of alternating residues of the carbohydrates N-acetyl glucosamine (GlcNAc) and N-acetyl muramic acid (MurNAc). Many of these chains run parallel to one another, and are connected with each other via a peptide moiety of the five amino acids L-Alanine-D-Glutamic acid-L-Lysine-D-Ala-D-Ala. The peptide cross-bridges connect the MurNAc residues on the glycan chains, resulting in a net-like structure. This meshwork that forms the bacterial cell wall imparts a great deal of structural support to the cell.
The bacterial peptidoglycan is synthesized in a series of steps that take place both inside and outside of the cell membrane. Just outside the membrane lie the transglycosylases, enzymes that put together GlcNAc-MurNAc subunits to form the glycan chains, and the transpeptidases, which perform the peptide cross-linking between these chains. The vancomycin family of antibiotics inhibits this stage of cell wall synthesis. While penicillin affects the active sites of the transpeptidase enzymes themselves, vancomycin binds to the peptide substrate and prevents it from binding to the enzyme’s active site. The bottom surface of vancomycin makes five hydrogen bonds to the D-Ala-D-Ala amino acids at the end of the peptide cross-bridges. By binding to these residues with high affinity, the antibiotic prevents them from being accessible to the active site of the transpeptidases. Peptide cross-linking therefore cannot occur, and the structural integrity of the peptidoglycan is compromised, causing the cell to lyse.
VRE bacteria actually only rarely cause illness in healthy humans. The problems occur when it has contact with an open wound or skin sore and VRE can then cause infection in the would or sore. On more rare occassions it can cause a serious infection of the blood or body tissues.
Vancomycin is a powerful antibiotic used in the treatment of such infections. Vancomycin is necessary to treat enterococci related infections because this bacteria is resistant to many other antibiotics. Of course, as you might gather from its name VRE can also become resistant to Vancomycin and the drug will not be successful and the infection will be very difficult to treat.
Vancomycin is a very important antibiotic and historically we can see why.
Throughout the twentieth century humans have fought hard against bacterial infections and bacteria which themselves have retaliated by developing resistance to our antibiotics. Vancomycin, however, has been a key player in this war against bacterial pathogens; it has been so important, in fact, that it is often known as the “antibiotic of last resort.”
When no other drug works, this 1.5 kD glycopeptide is used to kill bacteria. It is the antibiotic to which many physicians have turned when fighting Staphylococcus aureus and Clostridium difficile. But now, forty years after the drug was introduced into the clinic, the medical community is facing an incipient crisis in the use of vancomycin. More and more bacteria are gaining resistance to a drug that is often still seen as the last hope when trying to cure a bacterial disease.
Vancomycin was introduced into hospitals by scientists more than forty years ago in response to new strains of Staphylococci that were growing resistant to penicillin. As the former wonder drug penicillin became increasingly ineffective in hospitals around the world, physicians began to see vancomycin as the new antibiotic that would keep humans ahead of bacterial pathogens. The introduction of methicillin decreased the use and importance of vancomycin for a few years; however, when methicillin-resistant S. aureus strains appeared in the past two decades, the glycopeptide antibiotic was reinstated as a therapeutic agent.
Vancomycin is now seen as the last-resort drug because it is often the last opportunity that a physician may have to eliminate a bacterial infection, since bacteria have become resistant to so many other drugs and antibiotics