Grigor'eva Alina E, Bardasheva Alevtina V, Ryabova Elena S, Tupitsyna Anastasiya V, Zadvornykh Danila A, Koroleva Lyudmila S, Silnikov Vladimir N, Tikunova Nina V, Ryabchikova Elena I
Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of Russian Academy of Science, Lavrent'ev av., 8, 630090 Novosibirsk, Russia.
Microorganisms. 2023 Aug 30;11(9):2192. doi: 10.3390/microorganisms11092192.
The purposeful development of synthetic antibacterial compounds requires an understanding of the relationship between effects of compounds and their chemical structure. This knowledge can be obtained by studying changes in bacteria ultrastructure under the action of antibacterial compounds of a certain chemical structure. Our study was aimed at examination of ultrastructural changes in cells caused by polycationic amphiphile based on 1,4‒diazabicyclo[2.2.2]octane (DL12), ciprofloxacin and their hybrid (DLCip6); the samples were incubated for 15 and 45 min. DL12 first directly interacted with bacterial cell wall, damaging it, then penetrated into the cell and disrupted cytoplasm. Ciprofloxacin penetrated into cell without visually damaging the cell wall, but altered the cell membrane and cytoplasm, and inhibited the division of bacteria. The ultrastructural characteristics of cells damaged by the hybrid clearly differed from those under ciprofloxacin or DL12 action. Signs associated with ciprofloxacin predominated in cell damage patterns from the hybrid. We studied the effect of ciprofloxacin, DL12 and their hybrid on biofilm morphology using paraffin sections. Clear differences in compound effects on biofilm (45 min incubation) were observed. The results obtained allow us to recommend this simple and cheap approach for the initial assessment of antibiofilm properties of synthesized compounds.
合成抗菌化合物的定向研发需要了解化合物的作用与其化学结构之间的关系。通过研究具有特定化学结构的抗菌化合物作用下细菌超微结构的变化,可以获得这方面的知识。我们的研究旨在考察基于1,4-二氮杂双环[2.2.2]辛烷的聚阳离子两亲物(DL12)、环丙沙星及其混合物(DLCip6)对细胞超微结构的影响;样本孵育15分钟和45分钟。DL12首先直接与细菌细胞壁相互作用,破坏细胞壁,然后进入细胞并破坏细胞质。环丙沙星在视觉上未损伤细胞壁的情况下进入细胞,但改变了细胞膜和细胞质,并抑制了细菌分裂。混合物损伤的细胞超微结构特征明显不同于环丙沙星或DL12作用下的细胞。在混合物造成的细胞损伤模式中,与环丙沙星相关的特征占主导。我们使用石蜡切片研究了环丙沙星、DL12及其混合物对生物膜形态的影响。观察到这些化合物对生物膜(孵育45分钟)的作用存在明显差异。所得结果使我们能够推荐这种简单且廉价的方法用于初步评估合成化合物的抗生物膜特性。