Drug modification or destruction Sample Clauses

Drug modification or destruction. Bacteria may produce a number of enzymes to modify or destroy antimicrobial agents that successfully enter the cell. A classic, well-characterized example is the nearly ubiquitous β-lactamase enzymes, which cleave the characteristic ring of β-lactam antibiotics such as penicillin (3). Penicillin disrupts cell wall synthesis by molecular mimicry of the D-Ala-D-Ala motif in penicillin binding proteins (PBPs) that form the peptidoglycan layer (265). The lactam ring binds the active site of PBPs and prevents cross-linking of N-acetylglucosamine and N-acetylmuramic acid, thereby preventing formation of the peptidoglycan layer (265). β-lactamases recognize and hydrolyze the lactam ring, rendering the antibiotic inactive (60). Strains of N. gonorrhoeae producing β-lactamase were first identified in the 1970s (12, 192). This TEM-1-type β-lactamase is carried on a 5.1 kb or 7.1 kb R plasmid containing a Tn2-transposable element that harbors the bla gene, encoding the x- xxxxxxxxx (00, 000, 000). It is thought that this plasmid was obtained from a horizontal gene transfer event from Haemophilus parainfluenzae (75, 203). While not all strains of N. gonorrhoeae produce β-lactamase, 50 - 80% of isolates in certain geographical areas such as Latin America and the Western Pacific may carry an R plasmid producing β- lactamase. Widespread β-lactamase producing strains render treatment with penicillin unreliable to ineffective.