Antibiotics interfering with bacterial cell wall

The enzymatic colorimetric format is followed by the Penzyme test. This test is a qualitative enzymatic assay for rapid detection of -lactam residues in milk (28-30). The detection principle of the Penzyme test is based on measurement of the degree of inactivation of the enzyme oo-carboxypeptidase is involved in the synthesis of the bacterial cell wall by -lactam antibiotics. These residues bind specifically with the enzyme and inactivate it, thus interfering with bacterial cell wall formation. 

The antibiotic fosfomycin works by interfering with bacterial cell-wall synthesis through oxacyclopropane ring opening. Thus, the enzyme crucial for wall construction is deactivated by reaction of the SH group of one of its cysteine amino acids (for structure, see Problem 45 of Chapter 2) with the strained ether function. 

Vancomycin is an especially useful antibiotic for treating infections in cancer patients on chemotherapy and renal patients on dialysis. Uniike mammalian celis, bacterial cells are surrounded by a fairly rigid celi wall, which is crucial to the bacterium s survivai. Vancomycin kills bacteria by interfering with their cell wall synthesis. 

P-lactam antibiotics, exert thek antibacterial effect by interfering with the synthesis of the bacterial cell wall. These antibiotics tend to be "kreversible" inhibitors of cell wall biosynthesis and they are usually bactericidal at concentrations close to thek bacteriostatic levels. Cephalospotins are widely used for treating bacterial infections. They are highly effective antibiotics and have low toxicity. 

Bacitracin (Fig. 4) is a cyclic peptide antibiotic. The lipid II molecule involved in the bacterial cell wall biosynthesis has a C55 isoprenyl pyrophosphate moiety that must be dephosphorylated so that it can reparticipate in another round of lipid II transfer. Bacitracin binds to the isoprenyl pyrophosphate and prevents the dephosphorylation which, in turn, blocks cell wall growth by interfering with the release of the muropeptide subunits to the outside of the bacterial cell membrane. Bacitracin inhibits similar reactions in eukaryotic cells. So, it is systemically toxic but is an effective and widely used topical antibiotic. 

The bacterial cell wall is a rigid outer layer that completely surrounds the cytoplasmic membrane. Penicillin and other betalactam antibiotics inhibit bacterial growth by interfering with a specific step in bacterial cell wall synthesis. Penicillins are classified as in table 9.3.1. 

These /3-lactam antibiotics apparently work by interfering with the synthesis of bacterial cell walls. Figure 21-11 shows how the carbonyl group of the /3-lactam acy-lates a hydroxyl group (from a serine residue) on one of the enzymes involved in making the cell wall. The acylated enzyme is inactive for synthesis of the cell wall protein. This acylation step is unusual because it converts an amide to an ester, an uphill reaction that we would assume to be endothermic. With this /3-lactam, however, the strain of the four-membered ring activates the amide enough for it to acylate an alcohol to form an ester in an exothermic step. 

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