Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai, India.
Molecular Biophysics Unit, Indian Institute of Science, Bangalore, India.
IUBMB Life. 2020 May;72(5):978-990. doi: 10.1002/iub.2234. Epub 2020 Jan 26.
The assembly and disassembly of FtsZ play an essential role in bacterial cell division. Using single-cell imaging, we report that short exposure to BT-benzo-29 inhibits Z-ring formation in live Bacillus subtilis cells. Fluorescence recovery after photobleaching of the Z-ring in live bacteria demonstrated that BT-benzo-29 strongly suppressed the assembly dynamics of FtsZ in the Z-ring. Furthermore, B. subtilis cells expressing V275A-FtsZ resisted the antibacterial activity of BT-benzo-29 providing evidence that BT-benzo-29 inhibits bacterial proliferation by targeting FtsZ. In addition, a brief (8 min) exposure of BT-benzo-29 destroyed the Z-ring without perturbing the localization of a late cell division protein, DivIVA, the nucleoid segregation, and membrane permeability. BT-benzo-29, when used in combination with vancomycin and polymyxin B (PMB), produced a much stronger inhibitory effect on Bacillus subtilis and Escherichia coli cells, respectively. The combination index of BT-benzo-29 with vancomycin and PMB was determined to be <1, suggesting that BT-benzo-29 exhibits synergistic inhibitory effects on bacterial proliferation when used along with these antibiotics.
FtsZ 的组装和拆卸在细菌细胞分裂中起着至关重要的作用。通过单细胞成像，我们报告说，短时间暴露于 BT-苯并-29 会抑制活枯草芽孢杆菌细胞中环形成。活细菌中环的光漂白荧光恢复表明，BT-苯并-29 强烈抑制了 Z 环中 FtsZ 的组装动力学。此外，表达 V275A-FtsZ 的枯草芽孢杆菌细胞抵抗 BT-苯并-29 的抗菌活性，这提供了证据表明 BT-苯并-29 通过靶向 FtsZ 抑制细菌增殖。此外，BT-苯并-29 的短暂（8 分钟）暴露会破坏 Z 环，而不会干扰晚期细胞分裂蛋白 DivIVA 的定位、核分离和膜通透性。BT-苯并-29 与万古霉素和多粘菌素 B（PMB）联合使用时，对枯草芽孢杆菌和大肠杆菌细胞分别产生了更强的抑制作用。BT-苯并-29 与万古霉素和 PMB 的组合指数被确定为 <1，表明当与这些抗生素一起使用时，BT-苯并-29 对细菌增殖表现出协同抑制作用。
