The beta-lactam ring is key to the mode of action of these drugs that target and inhibit cell wall synthesis by binding the enzymes involved in synthesis. Most bacterial cells cannot survive once they have lost the capacity to produce and maintain their peptidoglycan layer. The enzymes essential for this function are anchored in the cell membrane and as a group are referred to as penicillin-binding proteins, or PBPs. Bacterial species may contain between four and six different types of PBPs. The PBPs involved in cell wall cross-linking (i.e., transpeptidases) are often the most ical for survival. When beta-lactams bind to these fBPs, cell wall synthesis is essentially halted. Death results from osmotic instability caused by faulty cell wall synthesis, or the binding of the beta-lactam to PBP may Mgger a series of events that leads to autolysis and death *the cell.
Glycopeptides. Glycopeptides are the other major class of antibiotics that inhibit bacterial cell wall synthesis; vancomycin is the most commonly used agent in this class. Vancomycin is a large molecule and functions differently from beta-lactam antibiotics (Figure 11-3). This agent does not bind to PBPs but does bind to precursors of cell wall synthesis. The binding interferes with the ability of the PBP enzymes, such as transpeptidases and transglycosylases, to incorporate the precursors into the growing cell wall. With the cessation of cell wall synthesis, cell growth stops and death often follows. Because vancomycin has a different mode of action, the resistance to beta-lactam agents by gram-positive bacteria does not generally hinder vancomycin activity. However, because of its relatively large size, vancomycin cannot penetrate the outer membrane of most gram-negative bacteria to ch2oh yj c, ^^
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