The components of bacterial cell wall are very much appealing as antimicrobial targets because of their absence in human counterparts. It is possible to determine the site in the synthesis pathway at which an antimicrobial acts by measuring accumulation of precursors and blocks in development of immature and mature peptidoglycan.

    ß-Lactam antimicrobials are also known to act at cell wall synthesis. They are also known as transpeptidase inhibitors thus blocking the conversion of immature to mature peptidoglycan. Glycopeptides also act at cell wall synthesis. Examples of such as Vancomycin which bind tightly to the terminal 2 D-alanines of the side chains of the immature peptidoglycan. This also produces a block at the same step as the ß-lactams by producing a steric hindrance to transpeptidase action, thereby preventing conversion of immature to mature peptidoglycan.

Determinats of Bactericidal Activity

1. in Escherichia coli

Mutations causing an ampicillin-tolerance phenotype were mapped to a genetic locus, hipA which consists of 2 genes in an operon. Mutations in hipA that cause ampicillin tolerance produce a cold-sensitive block in cell division and synthesis of peptidoglycan and other macromolecules.

The pathway involving hipAB also appears to be involved in the bactericidal activity of quinolones.

2. in Streptococcus pneumoniae

Endogenous autolytic activity is important for the bactericidal activity of ß-lactam. ß-lactams appear to activate autolysins in addition to inactivating transpeptidases.

3. in Pneumococcal mutants -a Vancomycin resistance

3.1.                            VncS and VncR as components of pathways that mediates cell death in response to several diverse drug target interactions

Mutant identification of the gene for a histidine kinase was termed vncS, which is contiguous to a gene encoding a response regulator, vncR. Studies revealed that disruption of  vncS produces tolerance to vancomycin. Through this, it was postulated that vncS acts as a phosphatase that dephosphorylates VncR-P. The laboratory vncS mutant was reported to be tolerant to ß-lactams, aminoglycosides, and quinolones as well as vancomycin.