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Edited by Scott J. Hultgren, Washington University School of Medicine, St. Louis, MO, and approved August 28, 2018 (received for review February 7, 2018)
Significance
Escherichia coli secrete polysaccharides, protein adhesins, and fibers to promote adhesion and biofilm formation. Curli are functional amyloid fibers produced by many human and environmental E. coli isolates. Furthermore, we recently discovered that E. coli produces a chemically modified form of cellulose, phosphoethanolamine cellulose. Here, we use a custom-built live-cell monolayer rheometer, housed within a microscope, to examine curli-based adhesion and reveal the molecular role of the modified cellulose in influencing adhesion of uropathogenic E. coli to bladder epithelial cells. In a high-shear environment, phosphoethanolamine cellulose confers a mortar-like function in maintaining cellular association of curli. Curli are readily dissociated from the cell in the absence of cellulose. This approach is applicable to other cellular and host-pathogen interfaces.
Abstract
Uropathogenic Escherichia coli (UPEC) are the major causative agents of urinary tract infections, employing numerous molecular strategies to contribute to adhesion, colonization, and persistence in the bladder niche. Identifying strategies to prevent adhesion and colonization is a promising approach to inhibit bacterial pathogenesis and to help preserve the efficacy of available antibiotics. This approach requires an improved understanding of the molecular determinants of adhesion to the bladder urothelium. We designed experiments using a custom-built live cell monolayer rheometer (LCMR) to quantitatively measure individual and combined contributions of bacterial cell surface structures [type 1 pili, curli, and phosphoethanolamine (pEtN) cellulose] to bladder cell adhesion. Using the UPEC strain UTI89, isogenic mutants, and controlled conditions for the differential production of cell surface structures, we discovered that curli can promote stronger adhesive interactions with bladder cells than type 1 pili. Moreover, the coproduction of curli and pEtN cellulose enhanced adhesion. The LCMR enables the evaluation of adhesion under high-shear conditions to reveal this role for pEtN cellulose which escaped detection using conventional tissue culture adhesion assays. Together with complementary biochemical experiments, the results support a model wherein cellulose serves a mortar-like function to promote curli association with and around the bacterial cell surface, resulting in increased bacterial adhesion strength at the bladder cell surface.
Footnotes
- ↵1To whom correspondence may be addressed. Email: ggf{at}stanford.edu or cegelski{at}stanford.edu.
Author contributions: E.C.H., G.G.F., and L.C. designed research; E.C.H., A.A., C.C., and W.T. performed research; E.C.H., A.A., C.C., G.G.F., and L.C. analyzed data; and E.C.H., G.G.F., and L.C. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1801564115/-/DCSupplemental.
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Phosphoethanolamine cellulose enhances curli-mediated adhesion of uropathogenic Escherichia coli to bladder epithelial cells
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