Filamenting temperature-sensitive mutant Z (FtsZ) and DNA replication proteins

Bacterial FtsZ and DNA replication proteins are essential components of the bacterial life cycle, governing cytokinesis and genome duplication, respectively. FtsZ, a prokaryotic homolog of tubulin, is a GTPase that assembles into a contractile Z-ring at the mid-cell to initiate division (Erickson et al., 2010, Microbiol Mol Biol Rev). DNA replication proteins, such as DNA polymerase III, DnaB helicase, and the DnaN sliding clamp, form the replisome complex responsible for copying the bacterial chromosome (O'Donnell et al., 2013, Cold Spring Harb Perspect Biol). These proteins are highly conserved across diverse bacterial pathogens, making them attractive targets for novel antibiotics, especially against multi-drug resistant strains. Inhibitors like PC190723 target FtsZ to prevent Z-ring formation, leading to cell filamentation and death (Haydon et al., 2008, Science), while compounds like griselimycin target the DNA sliding clamp to halt replication (Kling et al., 2015, Science). Despite their potential, therapeutic development faces challenges such as ensuring selectivity over human homologs and overcoming the rapid evolution of bacterial resistance.

Other names

Bacterial cell division proteinsReplisome componentsFtsZDNA polymerase IIIDNA helicaseDNA primaseDnaN sliding clamp

Inhibition of FtsZ polymerization and GTPase activity; inhibition of DNA polymerase III activity; inhibition of DNA sliding clamp (DnaN) function.