Elevated shear stress protects Escherichia coli cells adhering to surfaces via catch bonds from detachment by soluble inhibitors.
Soluble inhibitors find widespread applications as therapeutic drugs to reduce the ability of eukaryotic cells, bacteria, or viruses to adhere to surfaces and host tissues. Mechanical forces resulting from fluid flow are often present under in vivo conditions, and it is commonly presumed that fluid flow will further add to the inhibitive effect seen under static conditions. In striking contrast, we discover that when surface adhesion is mediated by catch bonds, whose bond life increases with increased applied force, shear stress may dramatically increase the ability of bacteria to withstand detachment by soluble competitive inhibitors. This shear stress-induced protection against inhibitor-mediated detachment is shown here for the fimbrial FimH-mannose-mediated surface adhesion of Escherichia coli. Shear stress-enhanced reduction of bacterial detachment has major physiological and therapeutic implications and needs to be considered when developing and screening drugs.
Nilsson
Lina M
LM
Department of Materials, Laboratory for Biologically Oriented Materials, Swiss Federal Institute of Technology, Wolfgang-Pauli-Strasse 10, ETH Hönggerberg, HCI F443, CH-8093 Zürich, Switzerland.
Thomas
Wendy E
WE
Sokurenko
Evgeni V
EV
Vogel
Viola
V
D018830:Adhesins, Escherichia coli / Q000378:metabolism; D001422:Bacterial Adhesion / Q000187:drug effects*; D004926:Escherichia coli / Q000378:metabolism / Q000502:physiology*; D036781:Fimbriae Proteins / Q000378:metabolism; D018869:Heat-Shock Response; D008358:Mannose / Q000378:metabolism; D008766:Methylmannosides / Q000494:pharmacology*; D013314:Stress, Mechanical
D018830:Adhesins, Escherichia coli; D008766:Methylmannosides; C058769:fimH protein, E coli; D036781:Fimbriae Proteins; C008466:methylmannoside; D008358:Mannose