Measuring the Forces Involved in Polyvalent Adhesion of Uropathogenic Escherichia coli to Mannose-Presenting Surfaces

Mechanisms of bacterial pathogenesis have become an increasingly important subject as pathogens have become increasingly resistant to current antibiotics. The adhesion of microorganisms to the surface of host tissue is often a first step in pathogenesis and is a plausible target for new antiinfectiv...

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Published inProceedings of the National Academy of Sciences - PNAS Vol. 97; no. 24; pp. 13092 - 13096
Main Authors Liang, Michael N., Smith, Stephen P., Metallo, Steven J., Choi, Insung S., Prentiss, Mara, Whitesides, George M.
Format Journal Article
LanguageEnglish
Published United States National Academy of Sciences of the United States of America 21.11.2000
National Acad Sciences
National Academy of Sciences
The National Academy of Sciences
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Summary:Mechanisms of bacterial pathogenesis have become an increasingly important subject as pathogens have become increasingly resistant to current antibiotics. The adhesion of microorganisms to the surface of host tissue is often a first step in pathogenesis and is a plausible target for new antiinfective agents. Examination of bacterial adhesion has been difficult both because it is polyvalent and because bacterial adhesins often recognize more than one type of cell-surface molecule. This paper describes an experimental procedure that measures the forces of adhesion resulting from the interaction of uropathogenic Escherichia coli to molecularly well defined models of cellular surfaces. This procedure uses self-assembled monolayers (SAMs) to model the surface of epithelial cells and optical tweezers to manipulate the bacteria. Optical tweezers orient the bacteria relative to the surface and, thus, limit the number of points of attachment (that is, the valency of attachment). Using this combination, it was possible to quantify the force required to break a single interaction between pilus and mannose groups linked to the SAM. These results demonstrate the deconvolution and characterization of complicated events in microbial adhesion in terms of specific molecular interactions. They also suggest that the combination of optical tweezers and appropriately functionalized SAMs is a uniquely synergistic system with which to study polyvalent adhesion of bacteria to biologically relevant surfaces and with which to screen for inhibitors of this adhesion.
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To whom reprint requests should be addressed. E-mail: gwhitesides@gmwgroup.harvard.edu.
Contributed by George M. Whitesides
Present address: The Charles Stark Draper Laboratory, Inc., 555 Technology Square, Cambridge, MA 02139-3563.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.230451697