N-Glycosylation in Piroplasmids: Diversity within Simplicity

Florín-Christensen, Mónica; Rodríguez, Anabel Elisa; Suárez, Carlos E.; Ueti, Massaro W.; Delgado, Fernando; Echaide, Ignacio; Schnittger, Leonhard

doi:10.3390/pathogens10010050

Cited by 5 publications

(7 citation statements)

References 59 publications

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“…It is intriguing to see a significant structural diversity in the N-glycan precursors within a single genus. Structural diversity in the N-glycan precursors has also been found in the piroplasmids (Florin-Christensen et al, 2021). In fact, the N-glycosylation seems to be highly amendable for the protozoan parasites to adapt to varied parasitic lifestyles in diverse host environments (Mule et al, 2020;Toustou et al, 2022).…”

Section: Reconstruction Of the Glycosylation From The Cryptosporidium...mentioning

confidence: 99%

“…These include orthologs for subunits alpha (ribophorin I; cgd6_5070), beta (Wbp1p; cgd2_1650), gamma (cgd8_5220), delta (ribophorin II; cgd7_5080), epsilon (DAD1/ Ost2-like; cgd5_2300) and STT3 (cgd6_2040). The OST complex is slightly simpler than that in humans that contains two catalytic STT3 subunits (i.e., STT3A and STT3B), but more complex than those in the piroplasmids (Shrimal and Gilmore, 2019;Florin-Christensen et al, 2021).…”

Section: Reconstruction Of the Glycosylation From The Cryptosporidium...mentioning

confidence: 99%

“…The lack of enzymes to further process N-glycans in the Golgi is in fact a general feature in the apicomplexans based on the KEGG annotations and massspectrometric evidence for Cryptosporidium, Toxoplasma and Plasmodium (Priest et al, 2003;Fauquenoy et al, 2011;Haserick et al, 2017a;Haserick et al, 2017b). Hematozoa (e.g., Plasmodium, Babesia and Theileria) even make highly truncated N-glycans (i.e., NAc2 or Man 1 NAc 2 ), in which most Theileria species and B. microti also lost all OST/STT subunits (Figure 3) (Morotti et al, 2019;Florin-Christensen et al, 2021).…”

Section: Implication On the Parasite Biologymentioning

confidence: 99%

“…Mass spectrometry-based assays also showed that the glycans in C. parvum were much simpler than those in humans and animals ( Haserick et al, 2017a ; Haserick et al, 2017b ). Additionally, significant differences in the glycosylation pathways were known between apicomplexans and the hosts and among various apicomplexan lineages ( Liu et al, 2016 ; Florin-Christensen et al, 2021 ; Toustou et al, 2022 ). However, information on the glycosylation pathways in Cryptosporidium is fragmented in the literature.…”

Section: Introductionmentioning

confidence: 99%

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

Wang

Zhu

2022

Front. Mol. Biosci.

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Cryptosporidium is a genus of apicomplexan parasites infecting humans or other vertebrates. The majority of the Cryptosporidium species live in host intestines (e.g., C. parvum, C. hominis and C. ubiquitum), but there are a few gastric species (e.g., C. muris and C. andersoni). Among them, C. parvum 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 Cryptosporidium parasites remains sketchy and only a few studies have truly determined the glycoforms in the parasites. Here we reanalyzed the Cryptosporidium genomes and reconstructed the glycosylation pathways, including the synthesis of N- and O-linked glycans and GPI-anchors. In N-glycosylation, intestinal Cryptosporidium possesses enzymes to make a simple precursor with two terminal glucoses on the long arm (i.e., Glc2Man5GlcNAc2 vs. Glc3Man9GlcNAc2 in humans), but gastric species only makes a simpler precursor containing only the “core” structure (i.e., Man3GlcNAc2). There is an ortholog of glucosidase II (GANAB) in all Cryptosporidium 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 O-linked glycosylation, all Cryptosporidium species may attach one-unit HexNAc (GalNAc and GlcNAc) and two-unit Fuc-type (Man-Fuc) glycans to the target proteins. Cryptosporidium lacks enzymes to further process N- and O-glycans in the Golgi. The glycosylphosphatidylinositol (GPI)-anchor in Cryptosporidium is predicted to be unbranched and unprocessed further in the Golgi. Cryptosporidium can synthesize limited nucleotide sugars, but possesses at least 12 transporters to scavenge nucleotide sugars or transport them across the ER/Golgi membranes. Overall, Cryptosporidium makes much simpler glycans than the hosts, and the N-glycoforms further differ between intestinal and gastric species. The Cryptosporidium N- and O-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.

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Section: Reconstruction Of the Glycosylation From The Cryptosporidium...mentioning

confidence: 99%

Section: Reconstruction Of the Glycosylation From The Cryptosporidium...mentioning

confidence: 99%

Section: Implication On the Parasite Biologymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Wang

Zhu

2022

Front. Mol. Biosci.

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“…Additionally, contrary to B. bovis, B. microti does not have an oligosaccharyl transferase in charge of transferring a (NAcGlc) 2 moiety from a lipid-linked oligosaccharide to a nascent protein destined for the secretory pathway in the endoplasmic reticulum. Thus, a significant difference among B. bovis and B. microti is the lack of ability of the latter to produce N-glycosylated proteins [77].…”

Section: Comparison Between B Microti and B Bovis Functional Proteasesmentioning

confidence: 99%

In Silico Survey and Characterization of Babesia microti Functional and Non-Functional Proteases

et al. 2021

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Human babesiosis caused by the intraerythrocytic apicomplexan Babesia microti is an expanding tick-borne zoonotic disease that may cause severe symptoms and death in elderly or immunocompromised individuals. In light of an increasing resistance of B. microti to drugs, there is a lack of therapeutic alternatives. Species-specific proteases are essential for parasite survival and possible chemotherapeutic targets. However, the repertoire of proteases in B. microti remains poorly investigated. Herein, we employed several combined bioinformatics tools and strategies to organize and identify genes encoding for the full repertoire of proteases in the B. microti genome. We identified 64 active proteases and 25 nonactive protease homologs. These proteases can be classified into cysteine (n = 28), serine (n = 21), threonine (n = 14), asparagine (n = 7), and metallopeptidases (n = 19), which, in turn, are assigned to a total of 38 peptidase families. Comparative studies between the repertoire of B. bovis and B. microti proteases revealed differences among sensu stricto and sensu lato Babesia parasites that reflect their distinct evolutionary history. Overall, this data may help direct future research towards our understanding of the biology and pathogenicity of Babesia parasites and to explore proteases as targets for developing novel therapeutic interventions.

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The Piroplasmida Babesia, Cytauxzoon, and Theileria in farm and companion animals: species compilation, molecular phylogeny, and evolutionary insights

et al. 2022

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The order Piroplasmida, including the genera Babesia, Cytauxzoon, and Theileria is often referred to as piroplasmids and comprises of dixenous hemoprotozoans transmitted by ticks to a mammalian or avian host. Although piroplasmid infections are usually asymptomatic in wild animals, in domestic animals, they cause serious or life-threatening consequences resulting in fatalities. Piroplasmids are particularly notorious for the enormous economic loss they cause worldwide in livestock production, the restrictions they pose on horse trade, and the negative health impact they have on dogs and cats. Furthermore, an increasing number of reported human babesiosis cases are of growing concern. Considerable international research and epidemiological studies are done to identify existing parasite species, reveal their phylogenetic relationships, and develop improved or new drugs and vaccines to mitigate their impact. In this review, we present a compilation of all piroplasmid species, isolates, and species complexes that infect domestic mammals and which have been well defined by molecular phylogenetic markers. Altogether, 57 taxonomic piroplasmid entities were compiled, comprising of 43 piroplasmid species, 12 well-defined isolates awaiting formal species description, and two species complexes that possibly mask additional species. The extrapolation of the finding of at least 57 piroplasmid species in only six domestic mammalian groups (cattle, sheep, goat, horse, dog, and cat) allows us to predict that a substantially higher number of piroplasmid parasites than vertebrate host species exist. Accordingly, the infection of a vertebrate host species by multiple piroplasmid species from the same and/or different phylogenetic lineages is commonly observed. Molecular phylogeny using 18S rRNA genes of piroplasmids infecting domestic mammals results in the formation of six clades, which emerge due to an anthropocentric research scope, but not due to a possibly assumed biological priority position. Scrutinizing the topology of inferred trees reveals stunning insights into some evolutionary patterns exhibited by this intriguing group of parasites. Contrary to expectations, diversification of parasite species appears to be dominated by host-parasite cospeciation (Fahrenholz's rule), and, except for piroplasmids that segregate into Clade VI, host switching is rarely observed. When only domestic mammalian hosts are taken into account, Babesia sensu lato (s.l.) parasites of Clades I and II infect only dogs and cats, respectively, Cytauxzoon spp. placed into Clade III only infect cats, Theileria placed into Clade IV exclusively infect horses, wheras Theileria sensu stricto (s.s.) of Clade V infects only cattle and small ruminants. In contrast, Babesia s.s. parasites of Clade VI infect all farm and companion animal species. We outline how the unique ability of transovarial transmission of Babesia s.s. piroplasmids of Clade VI facilitates species diversification by host switching to other host vertebrate species. Finally, a deterioration o...

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N-Glycosylation in Piroplasmids: Diversity within Simplicity

Cited by 5 publications

References 59 publications

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

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

In Silico Survey and Characterization of Babesia microti Functional and Non-Functional Proteases

The Piroplasmida Babesia, Cytauxzoon, and Theileria in farm and companion animals: species compilation, molecular phylogeny, and evolutionary insights

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