Abstract
Nowadays, the emergence of multidrug-resistant bacterial strains initiates the urgent need for the elucidation of the new drug targets for the discovery of antimicrobial drugs. Filamenting temperature-sensitive mutant Z (FtsZ), a eukaryotic tubulin homolog, is a GTP-dependent prokaryotic cytoskeletal protein and is conserved among most bacterial strains. In vitro studies revealed that FtsZ self-assembles into dynamic protofilaments or bundles and forms a dynamic Z-ring at the center of the cell in vivo, leading to septation and consequent cell division. Speculations on the ability of FtsZ in the blockage of cell division make FtsZ a highly attractive target for developing novel antibiotics. Researchers have been working on synthetic molecules and natural products as inhibitors of FtsZ. Accumulating data suggest that FtsZ may provide the platform for the development of novel antibiotics. In this review, we summarize recent advances in the properties of FtsZ protein and bacterial cell division, as well as in the development of FtsZ inhibitors.
Highlights
The antibacterial resistance phenomenon has seen an increase to dangerous, unprecedented levels in practically all parts of the world over the past 20 years
Totarol is a diterpenoid phenol isolated from Podocarpus totara that impedes the growth of many Gram-positive bacteria, including M. tuberculosis, which leads to the inhibition of Filamenting temperature-sensitive mutant Z (FtsZ) polymerization and prevention of its GTPase activity
Several bacterial cell division proteins with similar or novel functions have recently been explored to possess a key role in antibiotic discovery
Summary
The antibacterial resistance phenomenon has seen an increase to dangerous, unprecedented levels in practically all parts of the world over the past 20 years. Filamenting temperature-sensitive mutant Z (FtsZ) is a key cytoskeletal cell division protein in most bacteria. Scientists at the Southern Research Institute screened the library of 200 2-alkoxycarbonylamin-o-pyridine compounds, which are inhibitors of tubulin polymerization, to inhibit FtsZ and control M. tuberculosis growth. Colchicine, a well-recognized tubulin inhibitor, along with the compound 2-alkoxycarbonylamin-o-pyridine SRI-3072 and SRI-7614, inhibited the polymerization and GTP hydrolysis of M. tuberculosis FtsZ in a dependent manner.
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