Keren-Paz Alona, Brumfeld Vlad, Oppenheimer-Shaanan Yaara, Kolodkin-Gal Ilana
1Department of Molecular Genetics, Weizmann Institute of Science, 76100 Rehovot, Israel.
2Chemical Research Support, Weizmann Institute of Science, 76100 Rehovot, Israel.
NPJ Biofilms Microbiomes. 2018 Apr 17;4:8. doi: 10.1038/s41522-018-0051-8. eCollection 2018.
In nature, bacteria predominantly exist as highly structured biofilms, which are held together by extracellular polymeric substance and protect their residents from environmental insults, such as antibiotics. The mechanisms supporting this phenotypic resistance are poorly understood. Recently, we identified a new mechanism maintaining biofilms - an active production of calcite minerals. In this work, a high-resolution and robust µCT technique is used to study the mineralized areas within intact bacterial biofilms. µCT is a vital tool for visualizing bacterial communities that can provide insights into the relationship between bacterial biofilm structure and function. Our results imply that dense and structured calcium carbonate lamina forms a diffusion barrier sheltering the inner cell mass of the biofilm colony. Therefore, µCT can be employed in clinical settings to predict the permeability of the biofilms. It is demonstrated that chemical interference with urease, a key enzyme in biomineralization, inhibits the assembly of complex bacterial structures, prevents the formation of mineral diffusion barriers and increases biofilm permeability. Therefore, biomineralization enzymes emerge as novel therapeutic targets for highly resistant infections.
在自然界中，细菌主要以高度结构化的生物膜形式存在，生物膜由细胞外聚合物维系在一起，并保护其中的微生物免受环境侵害，如抗生素的影响。目前人们对这种表型抗性的支持机制了解甚少。最近，我们发现了一种维持生物膜的新机制——方解石矿物的主动生成。在这项研究中，我们使用了一种高分辨率且强大的显微CT技术来研究完整细菌生物膜内的矿化区域。显微CT是一种观察细菌群落的重要工具，它能够为细菌生物膜结构与功能之间的关系提供见解。我们的研究结果表明，致密且结构化的碳酸钙薄片形成了一个扩散屏障，保护生物膜菌落的内部细胞团。因此，显微CT可用于临床环境中预测生物膜的渗透性。研究表明，对生物矿化中的关键酶脲酶进行化学干扰，会抑制复杂细菌结构的组装，阻止矿物扩散屏障形成，并增加生物膜的渗透性。因此，生物矿化酶成为高度耐药感染新的治疗靶点。
