6 - The Relationship between Inhibition of Cell Wall Synthesis and Bacterial Lethality

Abstract

This chapter focuses on the relationship between inhibition of cell wall synthesis and bacterial lethality. In attempts to determine how β-lactams exert their biological effects, considerable efforts have been made to compare the kinetics of killing with the kinetics of other events such as changes in culture turbidity and synthesis of peptidoglycan and other cellular macromolecules. The inability to define the precise association of molecular events with the lethal action of antibiotics complicates an understanding of the mechanisms by which cell-wall inhibitors work and is consistent with the proposal that growth inhibition precedes lethal events. The consequences of cell-wall antibiotic interactions with susceptible cells can be categorized as lytic death, death in the absence of cellular lysis, or bacteriostasis. The assembly of an intact cell wall by growing streptococci requires precisely timed, sequentially changing events that are closely coupled to other events in the cell-division cycle. The hypothesis that a lesion occurs in the wall-membrane synthetic complex, possibly in the form of strategically located nicks in the peptidoglycan molecule, results in the temporal and/or spatial disorganization of the final stages of the wall assembly.