Antibodies damage fimbrial resilience, causing them to be stiff and tangled: Antibodies stiffen adhesion pili
2016 (English)In: Journal of Bacteriology, ISSN 0021-9193, E-ISSN 1098-5530Article in journal (Refereed) Accepted
Since adhesion fimbriae are a major virulence factor for many pathogenic Gram-negative bacteria, they are potential targets for antibodies. Fimbriae are commonly required to initiate colonization leading to disease, and their success as adhesion organelles lies in their ability to both initiate and sustain bacterial attachment to epithelial cells. The ability of fimbriae to unwind and rewind their helical filament presumably reduces their detachment from tissue surfaces during shear forces that accompany significant fluid flow. Disruption of functional fimbriae by inhibiting this resilience therefore should have great vaccine potential for prevention of disease. In this study, we show that two characteristic biomechanical features of fimbrial resilience, the extension force and the extension length, are significantly altered by antibody-binding to fimbriae. Fimbriae studied are normally expressed on enterotoxigenic Escherichia coli that are a major cause of diarrheal disease. This alteration in biomechanical properties was observed with bivalent polyclonal anti-fimbrial antibodies that recognize major pilin subunits, but not with Fab fragments of these antibodies. Thus, we propose that the mechanism by which bound antibodies disrupt natural fimbria uncoiling under force is by clamping together layers of the helical filament, thereby increasing their stiffness and reducing their resilience during fluid flow. In addition, we propose that antibodies tangle fimbriae via bivalent binding, by binding to two individual fimbriae and linking them together. Use of antibodies to disrupt physical properties of fimbriae may be generally applicable to the large number of Gram-negative bacteria that rely on these surface-adhesion molecules as an essential virulence factor.
Place, publisher, year, edition, pages
pili, IgG, vaccine, CFA/I, CS2, optical tweezers
Biophysics Immunology Other Physics Topics
IdentifiersURN: urn:nbn:se:umu:diva-126565OAI: oai:DiVA.org:umu-126565DiVA: diva2:1034041
FunderSwedish Research Council, 621- 2013-5379Swedish Research Council, 2012-4638NIH (National Institute of Health), RR025434