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 antibiot ics. 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 e 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 pro cedure that measures the forces of adhesion resulting from the interaction of uropathogenic Escherichia coli to molecularly well defined models of cel lular surfaces. This procedure uses self-assembled monolayers (SAMs) to mod el the surface of epithelial cells and optical tweezers to manipulate the b acteria. Optical tweezers orient the bacteria relative to the surface and, thus, limit the number of points of attachment (that is, the valency of att achment). Using this combination, it was possible to quantify the force req uired to break a single interaction between pilus and mannose groups linked to the SAM. These results demonstrate the deconvolution and characterizati on of complicated events in microbial adhesion in terms of specific molecul ar interactions. They also suggest that the combination of optical tweezers and appropriately functionalized SAMs is a uniquely synergistic system wit h which to study polyvalent adhesion of bacteria to biologically relevant s urfaces and with which to screen for inhibitors of this adhesion.