AUTHOR=Wang Dongqiang , Wang Chenchen , Zhu Guan 

TITLE=Genomic reconstruction and features of glycosylation pathways in the apicomplexan Cryptosporidium parasites

JOURNAL=Frontiers in Molecular Biosciences

VOLUME=9

YEAR=2022

URL=https://www.frontiersin.org/journals/molecular-biosciences/articles/10.3389/fmolb.2022.1051072

DOI=10.3389/fmolb.2022.1051072

ISSN=2296-889X

ABSTRACT=<p><italic>Cryptosporidium</italic> is a genus of apicomplexan parasites infecting humans or other vertebrates. The majority of the <italic>Cryptosporidium</italic> species live in host intestines (e.g., <italic>C. parvum</italic>, <italic>C. hominis</italic> and <italic>C. ubiquitum</italic>), but there are a few gastric species (e.g., <italic>C. muris</italic> and <italic>C. andersoni</italic>). Among them, <italic>C. parvum</italic> is the most important zoonotic species, for which a number of glycoproteins have been reported for being involved in the interacting with host cells. However, little is known on the cryptosporidium glycobiology. Information on the glycosylation pathways in <italic>Cryptosporidium</italic> parasites remains sketchy and only a few studies have truly determined the glycoforms in the parasites. Here we reanalyzed the <italic>Cryptosporidium</italic> genomes and reconstructed the glycosylation pathways, including the synthesis of <italic>N</italic>- and <italic>O</italic>-linked glycans and GPI-anchors. In <italic>N</italic>-glycosylation, intestinal <italic>Cryptosporidium</italic> possesses enzymes to make a simple precursor with two terminal glucoses on the long arm (i.e., Glc<sub>2</sub>Man<sub>5</sub>GlcNAc<sub>2</sub> vs. Glc<sub>3</sub>Man<sub>9</sub>GlcNAc<sub>2</sub> in humans), but gastric species only makes a simpler precursor containing only the “core” structure (i.e., Man<sub>3</sub>GlcNAc<sub>2</sub>). There is an ortholog of glucosidase II (GANAB) in all <italic>Cryptosporidium</italic> species, for which the authenticity is questioned because it contains no signal peptide and exist in gastric species lacking terminal glucoses for the enzyme to act on. In <italic>O</italic>-linked glycosylation, all <italic>Cryptosporidium</italic> species may attach one-unit HexNAc (GalNAc and GlcNAc) and two-unit Fuc-type (Man-Fuc) glycans to the target proteins. <italic>Cryptosporidium</italic> lacks enzymes to further process <italic>N</italic>- and <italic>O</italic>-glycans in the Golgi. The glycosylphosphatidylinositol (GPI)-anchor in <italic>Cryptosporidium</italic> is predicted to be unbranched and unprocessed further in the Golgi. <italic>Cryptosporidium</italic> can synthesize limited nucleotide sugars, but possesses at least 12 transporters to scavenge nucleotide sugars or transport them across the ER/Golgi membranes. Overall, <italic>Cryptosporidium</italic> makes much simpler glycans than the hosts, and the <italic>N-</italic>glycoforms further differ between intestinal and gastric species. The <italic>Cryptosporidium N</italic>- and <italic>O</italic>-glycans are neutrally charged and have limited capacity to absorb water molecules in comparison to the host intestinal mucins that are negatively charged and highly expandable in waters.</p>