Lectins as Promising Therapeutics for the Prevention and Treatment of HIV and Other Potential Coinfections

Mazalovska, Milena; Kouokam, J. Calvin

Urinary tract infections (UTIs) are among the most common bacterial infections and show elevated prevalence rates in women and HIV positive individuals [94] . Glycoproteins have been shown to be involved in the transmission of bacterial pathogens. For instance, uropathogenic E. coli (UPEC), which causes the majority of urinary tract infections (UTIs), need to overcome the constant shear stress of urine flow. This is accomplished by bacterial attachment to the renal epithelium via the attachment organelles types 1 and P fimbriae [95] . More than 90% of all UPEC strains express the adhesin FimH, one of the most described mannosespecific bacterial lectins expressed on the tip of type 1 fimbriae [95] [96] [97] . Meanwhile, use of lectins to achieve attachment to host cells is widely spread in bacterial organisms. Indeed, several bacteria bind to the cell glycocalyx for colonization, as is the case for cells in contact with the environment, for example, epithelial cells [98] . Lectins safely delivered to these surfaces targeted by microbial lectins would compete for the binding of bacteria and prevent adhesion, consequently suppressing colonization and infection. Interestingly, we recently demonstrated that GRFT administered parenterally was mainly eliminated through urine [99] , indicating that this molecule could help prevent colonization by competition with bacteria for the cell glycocalyx, especially those with mannose type lectins at the surface such as UPEC. Another lectin, Eutirucallin, isolated from the latex of Euphorbia tirucalli, also displays antimicrobial activity towards E. coli [100] . Chlamydia trachomatis, a critical etiologic agent of ocular and genital infections in humans, likely uses carbohydrates for attachment to host cells or entry. Three C. trachomatis glycoproteins, including the major outer membrane protein (MOMP; 40-kDa), a 32-kDa outer surface glycoprotein, and an 18-kDa molecule, have been reported [101, 102] . These surface exposed glycoproteins, especially, the MOMP, are critical for attachment and infectivity of C. trachomatis to HeLa cells, via their oligomannose-oligosaccharides [101] . It was reported that two plant lectins, including wheat germ agglutinin and Galanthus nivalis lectin, can block chlamydial attachment sites and inhibit infection in vitro [103, 104] .