Chemotherapy and therapeutic selectivity

In selected cases, chemotherapy targeted against many infectious agents has proven to be both extremely safe and efficacious. In these cases, therapeutic selectivity is achieved by exploiting qualitative differences in the structure, function, or intermediary metabolism between the target organism and the human cells.

Structural

Certain very safe and effective antibiotics therapeutically exploit the fact that bacteria require intact cell walls to maintain their integrity. Certain antibiotics can disrupt the formation or the integrity of the cell wall, causing the invading bacterium to become fragile and ultimately lyse. For example, peptidoglycan is a highly crosslinked, heteropolymeric component of the cell wall which is the molecular basis for its rigid structure. It is composed of linear chains of alternating units of N-acetylglucosamine and N-acetylmuramic acid which are linked by peptide crosslinks. The final phase of peptidoglycan synthesis is the crosslinking of the glycopeptide polymers by a transpeptidase reaction which occurs on the outside of the bacterial cell membrane. It appears that this transpeptidase step is inhibited by the beta-lactam antibiotics, such as the penicillins (i.e., penicillin G, V, ampicillin, oxacillin, etc.) and cephalosporins (i.e., cephapirin, cephalexin, cefaclor, cefotaxime, etc.). The beta-lactam antibiotics also bind to other bacteria-specific proteins (called penicillin-binding proteins, or PBP), which may significantly contribute to their antibacterial effects. Inhibition of the cell wall transpeptidase reaction and PBP binding causes the bacteria to lyse due to the autolytic activity of autolysins and murein hydrolases located in the cell wall.