The key bacterial cell division protein FtsZ as a novel antibacterial drug target

Abstract

The number of multidrug-resistant bacterial strains is currently increasing; thus, the determination of drug targets for the development of novel antimicrobial drugs is urgently needed. FtsZ, the prokaryotic homolog of the eukaryotic tubulin, is a GTP-dependent prokaryotic cytoskeletal protein that is conserved among most bacterial strains. In vitro studies revealed that FtsZ self-assembles into dynamic protofilaments or bundles, and it forms a dynamic Z-ring at the center of the cell, leading to septation and consequent cell division. The potential role of FtsZ in the blockage of cell division makes 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 on the properties of FtsZ protein and bacterial cell division, as well as on the development of FtsZ inhibitors.

A New Water-Soluble Bactericidal Agent for the Treatment of Infections Caused by Gram-Positive and Gram-Negative Bacterial Strains

“…Given the complex composition of IntegroPectins as compared to the commercial one highlighted by UV-vis and ATR-FTIR spectroscopic analyses, the superior antimicrobial activity against not only Gram-negative but also Gram-positive strains reasonably relies on a synergistic effect derived from the combined action of bioactive molecules (i.e., phenols, polyphenols, flavonoids, and terpenoids) and the pectic polysaccharides constituting this natural pectic extract, as opposed to commercial citrus pectins, which preferentially exert a bactericidal activity against Gram-negative bacteria only [ 60 ]. Among the numerous cellular targets of polyphenols, flavonoids, and terpenes [ 61 ], these compounds were shown to efficiently inhibit in vivo and in vitro the polymerization and the GTPase activity [ 62 ] of the filamenting temperature-sensitive mutant Z (FtsZ) protein (homolog to the eukaryotic tubulin), which is responsible for the bacterial cytokinesis [ 62 , 63 ], eventually leading to cell death. In this regard, the presence of either elongated bacterial cells or uncomplete division septa can be considered as a hallmark of an altered microbial morphology, underlining how the finely regulated cellular division process is perturbed.…”

A new water-soluble bactericidal agent for the treatment of polymicrobial infections

“…Given the complex composition of IntegroPectins as compared to the commercial one highlighted by UV-vis and ATR-FTIR spectroscopic analyses, the superior antimicrobial activity against not only Gram-negative but also Gram-positive strains reasonably relies on a synergistic effect derived from the combined action of bioactive molecules (i.e., phenols, polyphenols, flavonoids, and terpenoids) and the pectic polysaccharides constituting this natural pectic extract, as opposed to commercial citrus pectins, which preferentially exert a bactericidal activity against Gram-negative bacteria only [60]. Among the numerous cellular targets of polyphenols, flavonoids, and terpenoids [61], these compounds were shown to efficiently inhibit in vivo and in vitro the polymerization and the GTPase activity [62] of the filamenting temperature-sensitive mutant Z (FtsZ) protein (homolog to the eukaryotic tubulin), which is responsible for the bacterial cytokinesis [62][63], eventually leading to cell death. In this regard, the presence of either elongated bacterial cells or uncomplete division septa can be considered as a hallmark of an altered microbial morphology, underlining how the finely regulated cellular division process is perturbed.…”

Research Progress on Antibacterial Activities and Mechanisms of Natural Alkaloids: A Review

“…The FtsZ protein is essential for the cell cycle and, especially, the cell division in E. coli [ 78 ]. It participates in diaphragm formation and forms a ring structure at the division site to control the bacterial cell division process.…”