| As a crucial step in many bacterial infections, pathogens employ their adhesins that include lectins, to bind specific carbohydrates on the surface epithelium, mucous glycoproteins, and glycolipids of the host to get attached and start colonization (1,2). In the 'notorious' respiratory infections in cystic fibrosis (CF) patients, Pseudomonas aeruginosa, the major bacterial pathogen, is considered to utilize two lectins, LecA and LecB (also known as PA-IL and PA-IIL), together with some other carbohydrate-binding structures (adhesins), to bind certain sugars on the CF airway surface (3-6). For several reasons, the bacterial infection in CF lungs is extremely difficult, if not impossible, to be eliminated by any current antibiotics. In the pursuit of new anti-bacterial therapeutics, anti-adhesion therapy utilizing competitive carbohydrates to block the lectin-mediated bacterial binding offers a promising treatment for both CF and non-CF patients (7,8). Within the respiratory tract of CF patients, P. aeruginosa normally first appear as motile and non-mucoid, which is the typical morphology of environmental isolates. Over time, as a result of the environmental stresses and the formation of biofilms (9,10), clinically isolated P. aeruginosa often presents a wide range of phenotypic diversities, including the appearance of different colony morphologies, numerous physiological heterogeneities, and varied expression levels of virulence factors, to name a few (11,12). Lectins and other sugar-binding proteins are considered to be important virulence factors of P. aeruginosa, and their individual binding specificities have been extensively studied in the last several decades. However, the monosaccharide-binding profiles of different morphotypes haven't been thoroughly investigated on the cellular level. Due to the small sizes of the bacteria and low binding affinities of many lectins with monomeric carbohydrate ligands, studying bacterial carbohydrate-binding has always been challenging.;Therefore, the two major aims of this doctoral research project are: 1). Establish improved methodologies to investigate the lectin-mediated bacterial binding with carbohydrates. 2). Determine the monosaccharide-binding profiles of clinical CF P. aeruginosa isolates with different colony morphologies.. |
