The natural anthraquinone dye purpurin exerts antibacterial activity by perturbing the FtsZ assembly

Abstract

There is an increasing demand to discover novel antibacterial drugs to counter the ever-evolving genetic machinery of bacteria. The cell division protein FtsZ plays a vital role in bacterial cytokinesis and has been recognized as an effective antibacterial drug target. In this study, we have shown that the madder dye purpurin inhibited bacterial cytokinesis through perturbation of FtsZ assembly. Purpurin inhibited the growth of bacterial cells in a concentration-dependent manner and induced bacterial cell filamentation. Microscopy studies showed that it inhibited the localization of the Z ring at the midcell, and FtsZ was dispersed throughout the cells. Further, purpurin bound firmly to FtsZ with a dissociation constant of 11 µM and inhibited its assembly in vitro. It reduced the GTP hydrolysis by binding closer to the nucleotide-binding site of FtsZ. Purpurin inhibited the proliferation of mammalian cancer cells at higher concentrations without disturbing the polymerization of tubulin. The results collectively suggest that the natural anthraquinone purpurin can potently inhibit the growth of bacteria and serve as a lead molecule for the development of antibacterial agents.