Swammerdam Institute for Life Sciences, Department of Molecular Biology and Microbial Food Safety, University of Amsterdam, Science Park 904, 1098 XH, Amsterdam, The Netherlands.
Swammerdam Institute for Life Sciences, Department of Bacterial Cell Biology and Physiology, University of Amsterdam, Science Park 904, 1098 XH, Amsterdam, The Netherlands.
Sci Rep. 2018 Jun 14;8(1):9128. doi: 10.1038/s41598-018-27529-4.
An empirical approach was taken to screen a novel synthetic compound library designed to be active against Gram-positive bacteria. We obtained five compounds that were active against spores from the model organism Bacillus subtilis and the food-borne pathogen Bacillus cereus during our population based experiments. Using single cell live imaging we were able to observe effects of the compounds on spore germination and outgrowth. Difference in sensitivity to the compounds could be observed between B. subtilis and B. cereus using live imaging, with minor difference in the minimal inhibitory and bactericidal concentrations of the compounds against the spores. The compounds all delayed the bursting time of germinated spores and affected the generation time of vegetative cells at sub-inhibitory concentrations. At inhibitory concentrations spore outgrowth was prevented. One compound showed an unexpected potential for preventing spore germination at inhibitory concentrations, which merits further investigation. Our study shows the valuable role single cell live imaging can play in the final selection process of antimicrobial compounds.
采用经验方法筛选了一种新型的合成化合物库，旨在对革兰氏阳性菌具有活性。在基于群体的实验中，我们获得了五种对枯草芽孢杆菌和食源性病原菌蜡样芽孢杆菌孢子具有活性的化合物。使用单细胞实时成像，我们能够观察到化合物对孢子萌发和生长的影响。使用活细胞成像，可以观察到枯草芽孢杆菌和蜡样芽孢杆菌对化合物的敏感性存在差异，化合物对孢子的最小抑菌浓度和杀菌浓度略有差异。这些化合物都延迟了萌发孢子的破裂时间，并在亚抑制浓度下影响了营养细胞的代时。在抑制浓度下，孢子的生长被阻止。一种化合物在抑制浓度下显示出阻止孢子萌发的意外潜力，值得进一步研究。我们的研究表明，单细胞实时成像在抗菌化合物的最终选择过程中可以发挥重要作用。
