Targeting FtsZ for antibacterial therapy: a promising avenue.
The widespread problem of bacterial resistance towards existing drugs and the paucity of effective drugs for the treatment of bacterial infections have prompted the scientific community to think about novel strategies for discovering new classes of antibacterial drugs. Target-based screening of inhibitory molecules has emerged as an important alternative for the development of potent antibacterials. FtsZ is a prokaryotic cytoskeleton protein, which plays an important role in bacterial cell division. It forms a highly dynamic Z-ring at the centre of the cell and recruits other accessory proteins, which are involved in bacterial cytokinesis. Here, we discuss the assembly dynamics of FtsZ and the key features that place it among the novel antibacterial drug targets. The recent progress in finding the inhibitors of functional properties of FtsZ and its interactions with other proteins, which has been enabled by advanced screening methods and structure-based design, are presented herein. Although there are significant challenges in the development of this new class of antibacterial drugs, nonetheless the therapeutic potential of FtsZ as a drug target is motivating researchers to find lead molecules with enhanced efficacy and reduced toxicity.
Kapoor
Sonia
S
Indian Institute of Technology Bombay, School of Biosciences and Bioengineering, Mumbai 400076, India.
Panda
Dulal
D
D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000494:pharmacology*; D001424:Bacterial Infections / Q000188:drug therapy; D001426:Bacterial Proteins / Q000187:drug effects* / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000187:drug effects* / Q000378:metabolism; D016503:Drug Delivery Systems; D015195:Drug Design; D024881:Drug Resistance, Bacterial; D006801:Humans
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D003598:Cytoskeletal Proteins; C071525:FtsZ protein, Bacteria