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A Carbocyclic Curcumin Inhibits Proliferation of Gram-Positive Bacteria by Targeting FtsZ

Lookup NU author(s): Dr John Perry


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Inhibition of FtsZ assembly has been found to stall bacterial cell division. Here, we report the identification of a potent carbocyclic curcumin analogue (2d) that inhibits Bacillus subtilis 168 cell proliferation by targeting the assembly of FtsZ. 2d also showed potent inhibitory activity (minimum inhibitory concentrations of 2-4 mg/L) against several clinically important species of Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus. In addition, 2d displayed a significantly reduced inhibitory effect on human cervical cancer cells in comparison to its effect on bacterial cells. Using live cell imaging of GFP-FtsZ by confocal microscopy, 2d was found to rapidly perturb the cytokinetic FtsZ rings in Bacillus subtilis cells. The immunofluorescence imaging of FtsZ also showed that 2d destroyed the Z-ring in bacteria within S min. Prolonged treatment with 2d produced filamentous bacteria, but 2d had no detectable effect either on the nudeoids or on the membrane potential of bacteria. 2d inhibited FtsZ assembly in vitro, whereas it had minimal effects on tubulin assembly. Interestingly, 2d strongly enhanced the GTPase activity of FtsZ and reduced the GTPase activity of tubulin. Furthermore, 2d bound to purified FtsZ with a dissociation constant of 4.0-F 1.1 itM, and the binding of 2d altered the secondary structures of FtsZ. The results together suggested that the non-natural curcumin analogue 2d possesses powerful antibacterial activity against important pathogenic bacteria, and the evidence indicates that 2d inhibits bacterial proliferation by targeting FtsZ.

Publication metadata

Author(s): Groundwater PW, Narlawar R, Liao VWY, Bhattacharya A, Srivastava S, Kunal K, Doddareddy M, Oza PM, Mamidi R, Marrs ECL, Perry JD, Hibbs DE, Panda D

Publication type: Article

Publication status: Published

Journal: Biochemistry

Year: 2017

Volume: 56

Issue: 3

Pages: 514-524

Print publication date: 01/01/2017

Online publication date: 21/12/2016

Acceptance date: 02/04/2016

ISSN (print): 0006-2960

Publisher: American Chemical Society


DOI: 10.1021/acs.biochem.6b00879


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