John Samuelson

Research Description

Our lab studies the glycobiology of protozoan parasites that cause diarrhea (Cryptosporidium and Giardia), dysentery (Entamoeba), birth defects (Toxoplasma), and blindness (Acanthamoeba). In particular, we use mass spectrometric, biochemical, and genetic methods to characterize sugars added to glycoproteins, as well as the enzymes that make or remove these sugars (glycosyltransferases and glycosyl hydrolases, respectively). For example, we showed that asparagine-linked glycans (N-glycans) of Cryptosporidiumhave a single mannose arm that is hardly modified and so is distinct from complex, highly modified N-glycans of the host (ref. 1). In contrast, Cryptosporidiumvaccine candidates have mucin-like domains densely modified with O-GalNAc that resemble host intestinal mucins (ref. 2). We discovered a large set of nuclear proteins of Toxoplasmathat are decorated with O-linked fucose and showed that O-fucosyltransferase is a homolog of plant Spindly (refs. 3, 4). The host is lacking Spindly but has an O-GlcNAc transferase with a similar structure to Spindly that modifies an even larger set of nucleocytosolic proteins. We also identified a second Toxoplasma O-fucosyltransferase that modifies a secreted protein MIC2, which is essential for parasite adherence to and invasion into host cells (ref. 5).

The Samuelson lab also studies sugar polymers and glycoproteins present in cyst and oocyst walls of these parasites, which are critical for their transmission from person to person (refs. 6 to 8). The simple model we have developed is that these walls contain sugar polymers similar to those in fungal and plant walls: chitin (Entamoeba), glucan (Toxoplasma), and cellulose, chitin, and xylan (Acanthamoeba). In contrast to fungi and plants, glycoproteins in the parasite walls are few and are for the most part lectins (proteins that bind sugars), which bind the sugar polymers. These wall lectins are unique to each parasite and may be targets for diagnostic reagents. Finally, we have explored the potential use of alcohol-based hand sanitizers to prevent transmission of Giardia, Entamoeba, and Acanthamoeba (refs. 9, 10).

References

Complete bibliography can be viewed here.

1. Haserick JR, Leon D, Samuelson J, Costello CE. 2017. N-glycans of Cryptosporidium parvum contain a single mannose arm, are barely processed in the ER or Golgi, and show a strong bias for sites with threonine. Mol Cell Proteomics 16:S42-S53.  PubMed PMID: 28179475; PubMed Central PMCID: PMC5393390.
2. Haserick JR, Klein JA, Costello CE, Samuelson J. 2017. Cryptosporidium parvumvaccine candidates are incompletely modified with O-linked-N-acetylgalactosamine or contain N-terminal N-myristate and S-palmitate. PLoS One. 2017 12:e0182395. PubMed PMID: 28792526; PubMed Central PMCID: PMC5549699.
3. Bandini G, Haserick JR, Motari E, Ouologuem DT, Lourido S, Roos DS, Costello CE, Robbins PW, Samuelson J. 2016. O-fucosylated glycoproteins form assemblies in close proximity to the nuclear pore complexes of Toxoplasma gondii. Proc Natl Acad Sci USA 113:11567-11572.  PubMed PMID: 27663739; PubMed Central PMCID: PMC5068260.
4. Gas-Pascual E, Ichikawa HT, Sheikh MO, Serji MI, Deng B, Mandalasi M, Bandini G, Samuelson J, Wells L, West CM. 2019. CRISPR/Cas9 and glycomics tools for Toxoplasma glycobiology. J Biol Chem 294:1104-1125. PubMed PMID: 30463938; PubMed Central PMCID: PMC6349120.
5. Bandini G, Leon DR, Hoppe CM, Zhang Y, Agop-Nersesian C, Shears MJ, Mahal LK, Routier FH, Costello CE, Samuelson J. 2019. O-fucosylation of thrombospondin-like repeats is required for processing of microneme protein 2 and for efficient host cell invasion by Toxoplasma gondii J Biol Chem 294:1967-1983. PubMed PMID: 30538131; PubMed Central PMCID: PMC6369279.
6. Chatterjee A, Carpentieri A, Ratner DM, Bullitt E, Costello CE, Robbins PW, Samuelson J. 2010. Giardia cyst wall protein 1 is a lectin that binds curled fibrils of the GalNAc homopolymer. PLoS Pathogens 6: e1001059.  PubMed PMID: 20808847; PubMed Central PMCID: PMC2924369.
7. Bushkin GG, Motari E, Magnelli P, Gubbels MJ, Dubey JP, Miska KB, Bullitt E, Costello CE, Robbins PW, Samuelson J. 2012. β-1,3-glucan, which can be targeted by drugs, forms a trabecular scaffold in the oocyst walls of Toxoplasma and Eimeria. MBio 3:e00258-12.  PubMed PMID: 23015739; PubMed Central PMCID: PMC3518913.
8. Magistrado-Coxen P, Aqeel Y, Lopez A, Haserick JR, Urbanowicz BR, Costello CE, Samuelson J. 2019. The most abundant cyst wall proteins of Acanthamoeba castellaniiare lectins that bind cellulose and localize to distinct structures in developing and mature cyst walls. PLoS Negl Trop Dis 13:e0007352. PubMed PMID: 31095564; PubMed Central PMCID: PMC6541295.
9. Chatterjee A, Bandini G, Motari E, Samuelson J. 2015. Ethanol and isopropanol in concentrations present in hand sanitizers sharply reduce excystation of Giardia and Entamoeba and eliminate oral infectivity of Giardia cysts in gerbils. Antimicrob Agents Chemother 59:6749-6754. PubMed PMID: 27663739; PubMed Central PMCID: PMC5068260.
10. Aqeel Y, Rodriguez R Chatterjee A, Ingalls RR, Samuelson J. 2017. Killing of diverse eye pathogens (Acanthamoeba castellanii, Fusarium solani, and Chlamydia trachomatis) with alcohols. PLoS Negl Trop Dis 11:e0005382. PubMed PMID: 28182670; PubMed Central PMCID: PMC5321442.