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Published on: August 31, 2015
The natural anthraquinone dye purpurin exerts antibacterial activity by perturbing the FtsZ assembly
Susobhan Mahanty1, Krishnan Rathinasamy1
1School of Biotechnology, National Institute of Technology Calicut, Calicut, Kerala, India.
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.
Insights
The madder dye purpurin inhibits bacterial growth by disrupting cell division protein FtsZ assembly. This natural compound shows potential as a novel antibacterial agent lead molecule.
Area of Science:
- Microbiology
- Biochemistry
- Drug Discovery
Background:
- The rise of antibiotic resistance necessitates the discovery of novel antibacterial agents.
- The bacterial cell division protein FtsZ is a validated target for antibacterial drug development.
Purpose of the Study:
- To investigate the potential of the natural dye purpurin as an antibacterial agent by examining its effect on FtsZ.
Main Methods:
- Bacterial growth inhibition assays, microscopy to observe cell morphology and Z-ring localization, in vitro FtsZ assembly and GTPase activity assays.
- Purpurin's interaction with FtsZ was characterized by determining its dissociation constant.
- Mammalian cell proliferation assays were performed to assess potential toxicity.
Main Results:
- Purpurin inhibited bacterial growth in a dose-dependent manner and induced cell filamentation.
- Microscopy revealed disrupted Z-ring formation and FtsZ mislocalization.
- Purpurin bound to FtsZ (Kd = 11 µM), inhibited its in vitro assembly, and reduced GTP hydrolysis.
- High concentrations of purpurin inhibited cancer cell proliferation without affecting tubulin polymerization.
Conclusions:
- Purpurin effectively inhibits bacterial cytokinesis by targeting FtsZ assembly.
- The natural anthraquinone purpurin demonstrates potent antibacterial activity and serves as a promising lead for developing new antibacterial drugs.
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