Antibodies damage fimbrial resilience, making them stiff and tangled
(English)Manuscript (preprint) (Other academic)
Since adhesion fimbriae are a major virulence factor for many pathogenic Gram-negative bacteria, theyare potential targets for antibodies. Fimbriae are commonly required to initiate colonization leading todisease, and their success as adhesion organelles lies in their ability to both initiate and sustain bacterialattachment to epithelial cells. The ability of fimbriae to unwind and rewind their helical filament ispresumably reducing their detachment from tissue surfaces by shear forces during significant fluid flow.Disruption of functional fimbriae by inhibiting this resilience therefore should have great therapeuticpotential. In this study, we show that two characteristic biomechanical features of fimbrial resilience, theextension force and the extension length, are significantly altered by antibody-binding to fimbriaenormally expressed on enterotoxigenic Escherichia coli that are a major cause of diarrheal disease. Thiseffect was observed with bivalently binding polyclonal anti-fimbrial antibodies but not with Fab fragmentsrecognizing major pilin subunits. Thus, we propose that the mechanism by which bound antibodies disruptnatural fimbria uncoiling under force is by clamping together layers of the helical filament, therebyincreasing their stiffness and reducing their resilience during fluid flow. In addition, we propose thatantibodies tangle fimbriae via bivalent binding, by binding to two individual fimbriae and linking themtogether. Use of antibodies to disrupt physical properties of fimbriae may be generally applicable to thelarge number of Gram-negative bacteria that rely on these surface-adhesion molecules as an essentialvirulence factor.
pili, IgG, vaccine, CFA/I, CS2, optical tweezers
IdentifiersURN: urn:nbn:se:umu:diva-119692OAI: oai:DiVA.org:umu-119692DiVA: diva2:922835