Kristian SA, Hwang JH, Hall B, Leire E, Iacomini J, et al.
Journal of molecular medicine (Berlin, Germany) •
The ever-increasing threat of multi-drug resistant bacterial infections has spurred renewed interest in alternative approaches to classical antibiotic therapy. In contrast to other mammals, humans do not express the galactose-α-1,3-galactosyl-β-1,4-N-acetyl-glucosamine (α-Gal) epitope. As a result of exposure of humans to α-Gal in the environment, a large proportion of circulating antibodies are specific for the trisaccharide. In this study, we examine whether these anti-Gal antibodies can be recruited and redirected to exert anti-bacterial activity. We show that a specific DNA aptamer conjugated to an α-Gal epitope at its 5' end, herein termed an alphamer, can bind to group A Streptococcus (GAS) bacteria by recognition of a conserved region of the surface-anchored M protein. The anti-GAS alphamer was shown to recruit anti-Gal antibodies to the streptococcal surface in an α-Gal-specific manner, elicit uptake and killing of the bacteria by human phagocytes, and slow growth of invasive GAS in human whole blood. These studies provide a first in vitro proof of concept that alphamers have the potential to redirect pre-existing antibodies to bacteria in a specific manner and trigger an immediate antibacterial immune response. Further validation of this novel therapeutic approach of applying α-Gal technology in in vivo models of bacterial infection is warranted. . α-Gal-tagged aptamers lead to GAS opsonization with anti-Gal antibodies. . α-Gal-tagged aptamers confer phagocytosis and killing of GAS cells by human phagocytes. . α-Gal-tagged aptamers reduces replication of GAS in human blood. . α-Gal-tagged aptamers may have the potential to be used as novel passive immunization drugs.
The rat prostate gland is composed of several distinct lobes: the ventral, lateral, dorsal, and anterior (also called the coagulating gland). Each prostatic lobe is different in its morphology, secretions, and response to hormones. The present study characterized and compared the expression of glycoconjugates in three different lobes (ventral, lateral, and dorsal) of the Noble rat prostate gland by lectin histochemistry, using a battery of 30 different lectins. The results indicate that different prostatic lobes elaborate and secrete different glycoconjugates. The dorsal prostatic epithelium secretes mainly in an apocrine mode, as characterized by the presence of apical cytoplasmic blebs which are absent in the other two lobes, though merocrine secretion is also suggested. These cytoplasmic blebs were rich in Man, GlcNAc, Gal/GalNac, Fuc, NeuAc(alpha2,6)Gal, and oligosaccharides. Two types of cytoplasmic belbs were also identified according to their lectin bindings: blebs stained by S-Con A, LCA, PWA, UEA-II, RCA-I, DBA, ECA, WFA, Jacalin, MPA, SJA, LTA, UEA-I, PHA-E, and PHA-L, and some blebs stained by S-WGA, SBA, HAA, HPA, VAA, BPA, MAA, and SNA. The lectins, which reacted with the second type of blebs, also revealed some cytoplasmic granules in the dorsal prostatic epithelial cells. The epithelium of the lateral prostate showed weak or negative reactions to lectins, suggesting that it may express fewer glycoconjugates as compared to the other two lobes. The epithelial Golgi region of the ventral prostate is the most developed among the three lobes, and contained abundant GlcNAc, alpha/beta-GalNAc, and NeuAc(alpha2,6)Gal residues, as shown by its intense reactions to S-WGA, DBA, SBA, HAA, HPA, WFA, and SNA. GS-I-B4 reacted specifically with the basal epithelial cells in all three lobes, indicating that glycoconjugates with terminal alpha-Gal/GalNAc were commonly expressed in these basal cells. The basal cells in ventral prostate might express more complex glycoconjugates, as they were also stained by PWA, RCA-I, ECA, and PHA-L, in addition to GS-I-B4, suggesting that these basal cells contained more Gal(beta1,4)GlcNAc and Gal(beta1,4)GlcNAc(alpha1,2)Man residues. GS-I-B4 and PHA-L also demonstrated a differential staining of the stromal smooth muscles and their associated extracellular matrix in the three prostatic lobes, suggesting that these structural components in different prostatic lobes were different in their complex oligosaccharide contents, which probably has an influence on the epithelial-stromal interaction in the prostate. In summary, the present study has established for the first time the expression patterns of glycoconjugates in the three lobes of the Noble rat prostate gland and suggests that certain lectins are useful as histochemical markers for the three individual prostatic lobes.
