Curli Extracellular Matrix - The Functional Fold: Amyloid Structures in Nature - page 125

6,53-55

and factor XII) was suggested to deplete coagulation factors.

In addition, curli are able to activate plasminogen by capturing it
simultaneously with tissue plasminogen activator, leading to the
proximate degradation of soft tissues. Furthermore, curli interact

with molecules of the immune system, such as the Toll-like receptors
and major histocompatibility complex class I. The resulted activation
of the host innate immune system, as well as release of bradykinin,
stimulate the inflammatory response.

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14,54,57-59

Finally, several
findings notably indicated the role of curli in the infection process:
curli expressing strains, either pathogenic

or artificially expressing, display better adherence and invasion into
epithelial cells;

E . coli and S . typhimurium

41,50,51,59-61

inhibition of curli formation by rationally
designed peptides correlated with lower internalization rates;

34

and presence of curliated E . coli was related to sudden infant death

62

syndrome. Taken together, curli properties act to increase the

spread of bacteria to surrounding tissues, promote infections, and
contribute to the symptoms of sepsis.
The mechanism by which curli mediate invasion was proposed
to involve serum proteins binding, primarily fibronectin. When
inert particles such as latex beads are enveloped with fibronectin,
they can be taken up by cells.

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Curli fibres are assumed to take
advantage of this process, since a peptide containing the arginine-
glycine-aspartate (RGD) motif, responsible for interaction of
fibronectin with cellular integrins, was shown to strongly inhibit
curli-mediated internalization.

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In an attempt to determine the
regions within CsgA sequence that mediate binding to fibronectin,
two peptides corresponding to distant regions in the primary
sequence were identified, which were further shown to activate the
pro-inflammatory contact system. This substantiates that curli

functionality does not merely stem from the amyloid fold.

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7.6 Summary

Curli are an extraordinary example of how living microorganisms
harness the functional advantages offered by the amyloid fold, while
utterly dominating its formation and limiting its cellular toxicity.
These functional amyloids also demonstrate how specific properties
(as selective tissue binding or nucleation rather than polymerization
propensity) could be integrated into amyloidogenic sequences.