Abstract
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.
Highlights
Bacterial biofilms represent an important medical problem; the mechanisms of the onset of biofilm formation are poorly understood
We applied a range of pressures to the growth chamber layer that was filled with a green fluorescent dye and visualized the shapes of the roofs via 3-D reconstruction of the fluorescence distribution captured using confocal laser scanning microscopy (CLSM) (Supplementary Fig. 1b)
Since rpoH upregulation has been linked with the onset of biofilm formation in P. aeruginosa[27], we explored whether confinement-induced mechanical stress rendered uropathogenic E. coli (CFT073) colonies biofilm-like
Summary
Bacterial biofilms represent an important medical problem; the mechanisms of the onset of biofilm formation are poorly understood. The recurrence and persistence of bacterial urinary tract infections (UTIs) is ascribed to the ability of E. coli cells to invade epithelial cells lining the lumens of the urinary tract, to form tightly packed IBCs, and to disperse out of the host[3,4] These IBCs are structured as biofilms that have pod-like three-dimensional (3-D) appearances and express various extracellular matrix components, including elements of exopolysaccharide (EPS) and protein fibers (e.g., curli)[11,12]. Further analysis using a combination of mathematical modeling and experimental observations suggested a number of feedback mechanisms controlling the interplay between mechanical stress and biofilm formation, and cell survival under stressful conditions These results shed light on the mechanisms and consequences of biofilm formation and antibiotic tolerance during uropathogenic infections and, potentially, other instances of bacterial biofilms
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