The biomechanical and structural properties of CS2 fimbriae

TL;DR

This study characterizes the biomechanical properties of CS2 fimbriae from ETEC, revealing their low-force unwinding behavior and evolutionary adaptation, which may influence their role in gut colonization and pathogenicity.

Contribution

The paper provides the first detailed biophysical analysis of CS2 fimbriae, linking structural features to their biomechanical function and environmental adaptation in ETEC.

Findings

CS2 fimbriae unwind at 10 pN force

They have a corner velocity of 1300 nm/s

Biophysical properties classify them with low-force unwinding fimbriae

Abstract

Enterotoxigenic Escherichia coli (ETEC) are a major cause of diarrhea worldwide, and infection of children in underdeveloped countries often leads to high mortality rates. Isolated ETEC express a plethora of colonization factors (fimbriae/pili), of which CFA/I and CFA/II that are assembled via the alternate chaperone pathway (ACP), are amongst the most common. Fimbriae are filamentous structures, whose shafts are primarily composed of helically arranged single pilin-protein subunits, with a unique biomechanical capability allowing them to unwind and rewind. A sustained ETEC infection, under adverse conditions of dynamic shear forces, is primarily attributed to this biomechanical feature of ETEC fimbriae. Recent understandings about the role of fimbriae as virulence factors are pointing to an evolutionary adaptation of their structural and biomechanical features. In this work, we investigated the biophysical properties of CS2 fimbriae from the CFA/II group. Homology modelling its major structural subunit CotA reveals structural clues and these are related to the niche in which they are expressed. Using optical tweezers force spectroscopy we found that CS2 fimbriae unwind at a constant force of 10 pN and have a corner velocity of 1300 nm/s, i.e., the velocity at which the force required for unwinding rises exponentially with increased speed. The biophysical properties of CS2 fimbriae assessed in this work classify them into a low-force unwinding group of fimbriae together with the CFA/I and CS20 fimbriae expressed by ETEC strains. The three fimbriae are expressed by ETEC, colonize in similar gut environments, and exhibit similar biophysical features, but differ in their biogenesis. Our observation suggests that the environment has a strong impact on the biophysical characteristics of fimbriae expressed by ETEC.