Bacterial lectins, cell‐cell recognition and infectious disease

Abstract

Numerous bacterial strains produce surface lectins, commonly in the form of fimbriae that are filamentous assemblies of protein subunits. Among the best characterized of these are the type 1 (mannose specific) fimbrial lectins of Escherichia coli that consist almost exclusively of one class of subunit with a molecular mass of 17 kDa. They possess an extended combining site corresponding to a trisaccharide and preferentially bind carbohydrate units of oligomannose or hybrid type. Type 1 fimbriae also possess a hydrophobic region close to the carbohydrate-binding site, since aromatic a-mannosides inhibit strongly (up to lOOO-times more than methyl a-mannoside) the agglutination of yeasts by the bacteria and the adherence of the latter to pig ileal epithelial cells. The combining sites of type 1 fimbriae of the salmonellae and of other enteric bacteria are different from those of E. coli in that they are smaller and do not possess a hydrophobic region. The various bacterial surface lectins appear to function primarily in the initiation of infection by mediating bacterial adherence to epithelial cells, e.g. in the urinary and gastrointestinal tracts. The mannose specific lectins also act as recognition molecules in lectinophagocytosis (i.e. phagocytosis of the bacteria in the absence of opsonins) by mouse, rat and human peritoneal macrophages, and human polymorphonuclear leukocytes. Affinity chromatography of membrane lysates from human polymorphonuclear leukocytes on immobilized type 1 fimbrial lectin, using methyl u-mannoside as eluent, showed that glycoproteins with apparent molecular masses of 7&80, 100 and 150 kDa act as receptors for the bacteria. Inhibition experiments with monoclonal antibodies suggest that the glycoprotein bands of 100 and 150 kDa may be identical with the a and /l subunits of leukocyte complement receptors and adhesion glycoproteins involved in complement-mediated opsonophagocytosis. The systems described serve as a fine illustration for the biological role of lectin-carbohydrate interactions. Further studies of these systems will lead to a deeper understanding of the molecular basis of infectious diseases, and perhaps also to new approaches for their prevention.

Binding of plasminogen to Escherichia coli adhesion proteins

“…Type 1 fimbriae are commonly found and have a similar structure in most enterobacterial genera [15]; it can therefore be expected that the binding activity described here occurs in bacteria other than E. coli.…”

“…that totally inhibits the binding of type 1 fimbriae to eukaryotic cells and glycoproteins [15], and yeast cell agglutination by type I fimbriae was not inhibited by plasminogen at 100/~g/ml (not shown). On the other hand, treatment of type-l-fimbriated bacteria with activated plasmin (100/zg/ml for 2 h at 37°C) did not influence their ability to agglutinate yeast cells (not shown).…”

“…To investigate further this possibility, we have studied here the interaction of plasminogen with fimbriae found on Escherichia coli strains causing invasive infections. Fimbriae are protein filaments typically consisting of a major structural subunit and a few minor proteins including a lectin subunit which mediates bacterial attachment to host cells [15,16]. Recently, E. coli P fimbriae were found to bind to fibronectin via a mechanism that does not involve the lectin subunit [17], suggesting that bacterial fimbriae are multifunctional proteins with lectin-dependent and -independent functions.…”

Inhibition of EGFR pathway signaling and the metastatic potential of breast cancer cells by PA-MSHA mediated by type 1 fimbriae via a mannose-dependent manner

“…We reviewed the published literature and found that there was strong evidence for a positive link between adherence, the presence of fimbriae, and mannosebinding activity by bacteria (Harper et al, 1978;Ofek and Beachey, 1978;Sharon, 1987Sharon, , 2006. For several (Stepinska and Trafny, 1995;King et al, 2000;McEwan et al, 2008).…”

Catch Bond-mediated Adhesion without a Shear Threshold

“…This is thought to be due to the presence of an extended FimH binding pocket with multiple subsites corresponding to the size of a trimannose (3M) and, possibly, pentasaccharide (22)(23)(24). Indeed, although some lectins are capable of binding simple monosaccharides, it is rather typical for lectins to bind specifically to complex oligosaccharide ligands that ensure high affinity and specificity for cell-cell or cell-surface interactions (25).…”