TEN FEIZI BACTERIAL PATHOGENICITY Angling for recognition Bacterial proteins that mediate cell adhesion recognize specific cell surface oligosaccharides but only if the orientation of the oligosaccharide chain is appropriate. A diverse array of oligosaccharides attached to proteins as mannose-sensitive or mannose-inhibitable, fimbriae and lipids is prominently displayed at the surfaces of [7,8], which adhere to high-mannose type oligosaccha- cells, each differentiated cell-type having a characteris- rides of glycoproteins [9], and those of the P-type or tic repertoire. While the roles of specific oligosaccha- Pap fimbriae, which adhere to glycolipids of the globo ride sequences as ligands for endogenous proteins have series that contain the GalcC4Gal saccharide sequence only relatively recently begun to be defined (reviewed in [1,21), their ‘use’ as attachment sites by certain mi- [4,10,11]. In P-type IYmbriae, the carbohydrate-binding protein that mediates bacterial adherence is a minor crobes (several viruses, mycoplasmas and bacteria) has been more extensively documented. It is well appreci- ated among those in the field of microbial pathogenic- ity that carbohydrate-mediated adhesion to host cells is an important first event in the initiation of infection by such micro-org&isms, and in the selective binding to host cells of several toxins that bacteria produce [3,4]. Thus, the oligosaccharide repertoire on the host-cell sur- face, the nature of which is determined to a large ex- tent by the cellular complement of glycosyltransferase en- zymes, is among the key genetic susceptibility factors in microbial infection and toxin action. The saccharide recognition element on the host cell may be as small as a monosaccharide, such as sialic acid, joined by a specific linkage (2-3 or 2-6) to a subterminal galactose residue on the sugar chains of a multiplicity of glycoproteins and glycolipids. This is the case with influenza viruses [5]. At the other extreme, for the hu- man pathogen Mycoplasma pneumoniae, the receptors are long sialo-oligosaccharide sequences with sialic acid joined by 2-3 linkage to hexa- or octasaccharide back- bones that have a more restricted distribution among proteins and lipids [ 61. Adhesive proteins at the surface of bacteria occur either as integral components of tiamentous structllres (fim briae) or in the form of amorphous material. The fim- briae are heteropolymeric organelles consisting of he- lically arranged subunits, the biogenesis of each being the result of the coordinated action of a large gene clus- ter. The most extensively investigated fimbrial adhesive specificities are those of the so-called type 1, also known component at the fimbrial tip [12]; in type 1 firnbriae it is both at the tip and interspersed along the length of the limbria [13,14]. The carbohydrate-binding pro- teins at the tip of the P-type limbriae that occur on many strains of pathogenic Escherichia coli that cause urinary tract infections have been called G-adhesins. Nor- mark and associates have identified three classes of allelic variants of G-adhesin with Y&60% internal amino acid sequence homology and with differing fine specificities toward globo series glycolipids on eukaryotic cells [ 151. In an interesting extension of this discovery, the same group has now expressed a representative of each class of G-adhesins (PapGJgh, PapG,,10 and PrSGJ96) in E. coli HBlOl and tested them for their cell binding ability, using hemagglutination of a panel of erythrocytes from eleven animal species as the assay [16]. In addition, the authors evaluated the binding of the G-adhesins to glyco- lipids extracted from the same erythrocytes and resolved on silica gel chromatograms. The three G-adhesin vari- ants had overlapping specificities for globo series gly- colipids on the chromatogram: PapGJ96 and PapGADl10 bound strongly to all three globo series glycolipids - ceramide trisaccharide (GbO,), tetrasaccharide (Gb04) and pentasaccharide (GbO,) - whereas PrsGJg6bound strongly to GbO,, weakly to Gb04 but not to GbO, (Fig. 1 and 2). By contrast, the cell binding properties of the three adhesins were quite distinct: only PapGJs6induced agglutination of erythrocytes that are high expressors of the GbO,, only PapGADllo induced strong agglutination of erythrocytes having GbO* as the major glycolipid, and PrsG Gbd’ 6 alone agglutinated erythrOcjrteS Containing the 5. GbO, Gb04 GbOS GalNAc, N-acetylgalactosamine CAI, galactose GIG, Cer, glucose ceramicle L Volume 2 Number 4 1992 Fig. 1. Structures of the globo series gly- colipids. 185