Pathogenic Bacterial Sensors Based on Carbohydrates as Sensing Elements

Abstract

Protein–carbohydrate interactions are involved in a wide variety of cellular recognition processes including cell growth regulation, differentiation, adhesion, cancer cell metastasis, cellular trafficking, the immune response, and viral or bacterial infections. These specific interactions occur through glycoproteins, glycolipids, polysaccharides found on cell surfaces, and proteins with carbohydrate-binding domains called lectins through cooperative multiple interactions since it is known that individual carbohydrate–protein interactions are generally weak. A common way for bacteria to accomplish adhesion is through their cellular lectins, also called fimbriae or pili, which bind to complementary carbohydrates on the surface of the host tissues. Lectin-deficient mutant bacteria often fail to initiate infection. Carbohydrate-based detection of bacterial pathogens presents an exciting alternative to standard methods for screening and detecting bacterial targets in food industry, water and environment quality control, and clinical diagnosis. Conjugated fluorescent glycopolymers such as conjugated glycopoly(p-phenylene-ethynylene)s, glycopolythiophenes, glycopoly(p-phenylene)s, and carbohydrate-bearing polydiacetylenes have been prepared for quick detection of Escherichia coli (E. coli) through cooperative multivalent interactions between the polymeric carbohydrates and the bacterial pili because they combine fluorescent scaffolding and carbohydrate reporting functions into one package and possess intrinsic fluorescence and high sensitivity to minor external stimuli. Glyconanoparticles and galactose-functionalized carbon nanotubes (Gal-SWNTs) have been used as three-dimensional systems to study their specific multivalent interactions with E. coli. In addition, Gal-SWNTs have also been employed to detect Bacillus anthracis spores through divalent cation-mediated multivalent carbohydrate–carbohydrate interactions. Carbohydrate microarrays combine the benefits of immobilized format assays with the capability of detecting thousands of analytes simultaneously and can offer a general and powerful platform for whole-cell applications because their multivalent display of carbohydrates can mimic multivalent interactions at cell–cell interfaces. A simple but very effective diagnostic carbohydrate microarray has been reported for the quick detection of E. coli in complex biological mixtures with detection limit of 10⁵–10⁶ cells. Wang et al. reported another direct and unique approach to detect pathogenic bacteria by using a carbohydrate microarray of 48 carbohydrate-containing antigenic macromolecules for recognition of carbohydrate-binding antibodies from 20 human serum specimens.

Pathogenic bacteria possess a cell surface capsular polysaccharide (CPS) or lipopolysaccharide (LPS) shell, or both, which helps the pathogen initiate an infection. Lectin microarrays have been utilized as a very important and powerful tool to detect E. coli, profile diverse glycan structures of E. coli and discover dynamic changes in surface glycosylation of bacteria in response to environmental stimuli through specific multivalent interactions of lectins and the bacterial LPSs.