The Remarkable Biomechanical Properties of the Type 1 Chaperone-Usher Pilus: A Structural and Molecular Perspective

Abstract

Chaperone-usher (CU) pili are long, supramolecular protein fibers tethered to the surface of numerous bacterial pathogens. These virulence factors function primarily in bacterial adhesion to host tissues, but they also mediate biofilm formation. Type 1 and P pili of uropathogenic Escherichia coli (UPEC) are the two best-studied CU pilus examples, and here we primarily focus on the former. UPEC can be transmitted to the urinary tract by fecal shedding. It can then ascend up the urinary tract and cause disease by invading and colonizing host tissues of the bladder, causing cystitis, and the kidneys, causing pyelonephritis. FimH is the subunit displayed at the tip of type 1 pili and mediates adhesion to mannosylated host cells via a unique catch-bond mechanism. In response to shear forces caused by urine flow, FimH can transition from a low-affinity to high-affinity binding mode. This clever allosteric mechanism allows UPEC cells to remain tightly attached during periods of urine flow, while loosening their grip to allow dissemination through the urinary tract during urine stasis. Moreover, the bulk of a CU pilus is made up of the rod, which can reversibly uncoil in response to urine flow to evenly spread the tensile forces over the entire pilus length. We here explore the novel structural and mechanistic findings relating to the type 1 pilus FimH catch-bond and rod uncoiling and explain how they function together to enable successful attachment, spread, and persistence in the hostile urinary tract.

Coaggregation properties of trimeric autotransporter adhesins

“…It is interesting to note that on glass, agitation promoted biofilm formation by TAAs except EibA, which suggests that shear forces promote adhesion mediated by TAAs on this surface. Similar catch bond‐type behavior has been observed for several bacterial adhesins before (Dufrêne & Viljoen, 2020; Hospenthal & Waksman, 2019) and also the TAA AtaA from Acinetobacter sp. Tol 5 mediates stronger binding to glass surfaces and more aggregation under moderate shear stress (Furuichi, Iwasaki, & Hori, 2018).…”

FIMBRIAE AND FLAGELLA MEDIATED SURFACE MOTILITY AND THE EFFECT OF GLUCOSE ON NONPATHOGENIC AND UROPATHOGENICESCHERICHIA COLI

“…FimH might bind weakly to the agar, since the nonspecific binding of FimH to surfaces without mannose has been proposed (37). The basis for motility may be the inherent flexibility of components of the type 1 fimbriae (38). FimH, the mannose-binding lectin of the fimbriae, and FimA, the major fimbrial subunit, undergo large conformational changes in response to shear force.…”

“…If the mannose residues are not highly exposed, then fimbriated bacteria may move until a region is reached that has exposed mannose. Once bound, fimbriae binding and expression increase (38, 43). If this sequence of events occurs, then fimbriae-mediated motility could help establish some infections.…”

Deep mutational scanning of the Neisseria meningitidis major pilin reveals the importance of pilus tip‐mediated adhesion

“…The existence of a structurally distinct pilus tip is well characterized for other pilus type such as the chaperone-usher pilus present in uropathogenic E. coli (Hospenthal & Waksman, 2019). The ability of the SM1 antibody directed against a major pilin epitope to inhibit initial bacterial adhesion is in favor of this scenario.…”

“…The exact nature of the pilus tip is currently unclear, but this result is in contradiction with studies indicating that other proteins such as minor pilins associate with pili and could potentially form the pilus tip. The existence of a structurally distinct pilus tip is well characterized for other pilus type such as the chaperone-usher pilus present in uropathogenic E. coli (Hospenthal & Waksman, 2019). Electron microscopy images of type I pili show a thin tip fibrillum attached to the pilus itself.…”