Department of Biomedical Engineering, Yale University, New Haven, CT, 06520, USA.
Yale Systems Biology Institute, Yale University, West Haven, CT, 06516, USA.
Nat Commun. 2018 Oct 5;9(1):4087. doi: 10.1038/s41467-018-06552-z.
Bacterial biofilms represent an important medical problem; however, the mechanisms of the onset of biofilm formation are poorly understood. Here, using new controlled methods allowing high-throughput and reproducible biofilm growth, we show that biofilm formation is linked to self-imposed mechanical stress. In growing uropathogenic Escherichia coli colonies, we report that mechanical stress can initially emerge from the physical stress accompanying colony confinement within micro-cavities or hydrogel environments reminiscent of the cytosol of host cells. Biofilm formation can then be enhanced by a nutrient access-modulated feedback loop, in which biofilm matrix deposition can be particularly high in areas of increased mechanical and biological stress, with the deposited matrix further enhancing the stress levels. This feedback regulation can lead to adaptive and diverse biofilm formation guided by the environmental stresses. Our results suggest previously unappreciated mechanisms of the onset and progression of biofilm growth.
细菌生物膜是一个重要的医学问题，然而生物膜形成的机制还不甚清楚。在这里，我们使用新的、可实现高通量和可重复生物膜生长的控制方法，表明生物膜形成与自我施加的机械压力有关。在生长的尿路致病性大肠杆菌菌落中，我们报告说，机械压力最初可能来自于菌落被限制在微腔或水凝胶环境中时所伴随的物理压力，这种环境让人联想到宿主细胞的细胞质。然后，生物膜形成可以通过营养物质可访问性调节的反馈回路来增强，其中生物膜基质的沉积在机械和生物压力增加的区域特别高，而沉积的基质进一步增加了压力水平。这种反馈调节可以导致生物膜的适应性和多样化形成，由环境压力引导。我们的结果表明了生物膜生长开始和进展的以前未被认识的机制。
