FimH forms catch bonds that are enhanced by mechanical force due to allosteric regulation.
The bacterial adhesive protein, FimH, is the most common adhesin of Escherichia coli and mediates weak adhesion at low flow but strong adhesion at high flow. There is evidence that this occurs because FimH forms catch bonds, defined as bonds that are strengthened by tensile mechanical force. Here, we applied force to single isolated FimH bonds with an atomic force microscope in order to test this directly. If force was loaded slowly, most of the bonds broke up at low force (<60 piconewtons of rupture force). However, when force was loaded rapidly, all bonds survived until much higher force (140-180 piconewtons of rupture force), behavior that indicates a catch bond. Structural mutations or pretreatment with a monoclonal antibody, both of which allosterically stabilize a high affinity conformation of FimH, cause all bonds to survive until high forces regardless of the rate at which force is applied. Pretreatment of FimH bonds with intermediate force has the same strengthening effect on the bonds. This demonstrates that FimH forms catch bonds and that tensile force induces an allosteric switch to the high affinity, strong binding conformation of the adhesin. The catch bond behavior of FimH, the amount of force needed to regulate FimH, and the allosteric mechanism all provide insight into how bacteria bind and form biofilms in fluid flow. Additionally, these observations may provide a means for designing antiadhesive mechanisms.
Yakovenko
Olga
O
Department of Bioengineering, University of Washington, Seattle, Washington 98195, USA.
Sharma
Shivani
S
Forero
Manu
M
Tchesnokova
Veronika
V
Aprikian
Pavel
P
Kidd
Brian
B
Mach
Albert
A
Vogel
Viola
V
Sokurenko
Evgeni
E
Thomas
Wendy E
WE
D018829:Adhesins, Bacterial / Q000737:chemistry; D018830:Adhesins, Escherichia coli / Q000737:chemistry* / Q000502:physiology; D000494:Allosteric Regulation; D000495:Allosteric Site; D001422:Bacterial Adhesion; D004926:Escherichia coli / Q000378:metabolism*; D036781:Fimbriae Proteins / Q000737:chemistry / Q000502:physiology*; D015964:Gene Expression Regulation, Bacterial; D007700:Kinetics; D018625:Microscopy, Atomic Force; D008954:Models, Biological; D008956:Models, Chemical; D008968:Molecular Conformation; D011487:Protein Conformation; D013314:Stress, Mechanical
D018829:Adhesins, Bacterial; D018830:Adhesins, Escherichia coli; C058769:fimH protein, E coli; D036781:Fimbriae Proteins