BT-benzo-29 inhibits bacterial cell proliferation by perturbing FtsZ assembly

Ray, Shashikant and Jindal, Bhavya and Kunal, Kishore and Surolia, Avadhesha and Panda, Dulal (2015) BT-benzo-29 inhibits bacterial cell proliferation by perturbing FtsZ assembly. In: FEBS JOURNAL, 282 (20). pp. 4015-4033.

PDF FEBS_Jou_282-20-4015_2015.pdf - Published Version Restricted to Registered users only Download (3MB) | Request a copy

Abstract

We have identified a potent antibacterial agent N-(4-sec-butylphenyl)-2-(thiophen-2-yl)-1H-benzod]imidazole-4-carboxa mide (BT-benzo-29) from a library of benzimidazole derivatives that stalled bacterial division by inhibiting FtsZ assembly. A short (5 min) exposure of BT-benzo-29 disassembled the cytokinetic Z-ring in Bacillus subtilis cells without affecting the cell length and nucleoids. BT-benzo-29 also perturbed the localization of early and late division proteins such as FtsA, ZapA and SepF at the mid-cell. Further, BT-benzo-29 bound to FtsZ with a dissociation constant of 24 +/- 3 m and inhibited the assembly and GTPase activity of purified FtsZ. A docking analysis suggested that BT-benzo-29 may bind to FtsZ at the C-terminal domain near the T7 loop. BT-benzo-29 displayed significantly weaker inhibitory effects on the assembly and GTPase activity of two mutants (L272A and V275A) of FtsZ supporting the prediction of the docking analysis. Further, BT-benzo-29 did not appear to inhibit DNA duplication and nucleoid segregation and it did not perturb the membrane potential of B. subtilis cells. The results suggested that BT-benzo-29 exerts its potent antibacterial activity by inhibiting FtsZ assembly. Interestingly, BT-benzo-29 did not affect the membrane integrity of mammalian red blood cells. BT-benzo-29 bound to tubulin with a much weaker affinity than FtsZ and exerted significantly weaker effects on mammalian cells than on the bacterial cells indicating that the compound may have a strong antibacterial potential.

Item Type:	Journal Article
Publication:	FEBS JOURNAL
Publisher:	WILEY-BLACKWELL
Additional Information:	Copy right for this article belongs to the WILEY-BLACKWELL, 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
Keywords:	bacterial cell division; cytokinesis; fluorescence; membrane integrity; membrane potential
Department/Centre:	Division of Biological Sciences > Molecular Biophysics Unit
Date Deposited:	19 Nov 2015 04:51
Last Modified:	19 Nov 2015 04:51
URI:	http://eprints.iisc.ac.in/id/eprint/52767

Actions (login required)

View Item