A 60-year-old woman has been hospitalized for three weeks with widely metastatic ovarian adenocarcinoma, and she becomes septic with vancomycin-resistant enterococcus. What is the mechanism of vancomycin resistance in this organism?
High-Yield Explanation
The antibiotic propey of vancomycin depends upon its ability to bind D-ala-D-ala, which is vital in the synthesis of peptidoglycan peptide bridges. Vancomycin-resistant enterococci instead utilize D-lactic acid in their peptide bonds, and thus are resistant to the action of vancomycin. Enzymatic deactivation of antibiotics is a common mode of resistance to aminoglycosides, chloramphenicol, and sulfonamides. The most common chemical modifications are acetylation, adenylation, and phosphorylation. Penicillin that has penetrated the cell membrane is kept in place by binding to penicillin binding proteins (PBPs). Penicillin resistance may be conferred through altered PBP affinity or number. Vancomycin resistance does not depend on PBPs. beta-lactamase is a bacterial enzyme that inactivates some of the penicillins and cephalosporins, but has no activity on vancomycin. Ref: MacDougall C. (2011). Chapter 55. Protein Synthesis Inhibitors and Miscellaneous Antibacterial Agents. In L.L. Brunton, B.A. Chabner, B.C. Knollmann (Eds), Goodman & Gilman's The Pharmacological Basis of Therapeutics, 12e