South China Advanced Institute for Soft Matter Science and Technology, School of Molecular Science and Engineering, South China University of Technology, Guangzhou 510640, China; Guangdong Provincial Key Laboratory of Functional and Intelligent Hybrid Materiasls and Devices, South China University of Technology, Guangzhou 510640, China.
South China Advanced Institute for Soft Matter Science and Technology, School of Molecular Science and Engineering, South China University of Technology, Guangzhou 510640, China; Guangdong Provincial Key Laboratory of Functional and Intelligent Hybrid Materiasls and Devices, South China University of Technology, Guangzhou 510640, China.
J Inorg Biochem. 2021 Jul;220:111463. doi: 10.1016/j.jinorgbio.2021.111463. Epub 2021 Apr 15.
Developing strategies against the antibiotic resistance is a major global challenge for public health. Here, we report the synergy of the combination of Preyssler-type polyoxometalates (POMs) ([NaPWO] or [AgPWO]) and ribosome-targeting antibiotics for high antibacterial efficiency with low risk of antibiotic resistance. Due to their ultra-small sizes and active surface ligands, POM anions show strong affinity to bacterial cell membrane and impose hyperpolarization of the bacterial cells as well as the decrease of Mg influx by blocking Mg transporters, which finally lead to the structural perturbations of ribosomes and instability of bacterial structures. The bacterial growth can, therefore, be regulated by the presence of POMs: a fraction of Bacillus subtilis shifted to a 'dormant', slow-growing cellular state (an extended lag phase) upon the application of subinhibitory concentration of POMs. An approach to combat antibiotic resistant bacteria by applying POMs at their early growth phase followed by antibiotic exposure is validated, and its high efficiency for bacterial control is confirmed.
开发对抗抗生素耐药性的策略是公共卫生领域面临的重大全球挑战。在这里，我们报告了 Preyssler 型多金属氧酸盐（POM）（[NaPWO]或[AgPWO]）与核糖体靶向抗生素联合使用的协同作用，以实现高效的抗菌效果和低抗生素耐药风险。由于其超小尺寸和活性表面配体，POM 阴离子与细菌细胞膜具有很强的亲和力，并通过阻断镁转运体使细菌细胞发生超极化以及镁内流减少，从而导致核糖体的结构扰动和细菌结构的不稳定。因此，通过存在 POM 可以调节细菌的生长：在亚抑制浓度的 POM 存在下，一部分枯草芽孢杆菌转变为“休眠”、生长缓慢的细胞状态（延长的迟滞期）。通过在细菌早期生长阶段应用 POM 然后暴露于抗生素来对抗抗生素耐药菌的方法得到了验证，并证实了其对细菌控制的高效性。
