Entamoeba histolytica, Giardia lamblia, and Trichomonas are simple eukaryotes, which cause dysentery, diarrhea, and vaginitis, respectively. Our laboratory uses molecular biological methods to study the biochemistry, cell biology, pathogenesis, and evolution of these important human pathogens.
One project attempts to determine the composition of the walls of Entamoeba cysts, which are the infectious and diagnostic form. Chitin in cyst wall is made by stage-specific chitin synthases and is modified by endogenous chitin deacetylases and chitinases. Chitin fibrils in the wall are held together unique lectins , which have multiple chitin-binding domains. Post-translation modifications of the cyst wall lectins include addition of unusual O-phosphodiester-linked sugars and cleavages between chitin-binding domains. Identification of these cyst wall-associated lectins may lead to better diagnostic reagents for distinguishing pathogenic from non-pathogenic amebae.
A second project, which is performed in collaboration with my colleague Phillips Robbins, attempts to understand Asn-linked glycosylation in Entamoeba, Giardia, and other protists . In particular, we use bioinformatics to predict lipid-linked N-glycan precursors, as well as N-glycan associated proteins involved in quality control in the ER lumen. We test our predictions using biochemical methods, which include determinations of carbohydrate structures and purification of glycoproteins by lectin columns. These studies suggest 1) the present diversity of N-glycans derives in part from secondary loss of genes encoding enzyme involved in N-glycan precursor synthesis, 2) protists with short N-glycans lack N-glycan-dependent quality control, and 3) there is Darwinian selection for sites of N-glycans in secreted proteins of diverse eukaryotes and viruses. Unique parasite sugars may be novel vaccine candidates or targets for anti-microbial lectins.
A third project is concerned with how Entamoeba, Giardia, and Trichomonas adapt to the anaerobic environment in the intestinal lumen. We have identified an atrophic mitochondrion-derived organelle, which lacks enzymes of oxidative phosphorylation in Entamoeba. We have also identified numerous bacterium-like fermentation enzymes in these protists, which appear to have been obtained by lateral gene transfer (LGT). Although LGT is frequent between bacteria, it is unusual between bacteria and eukaryotes. Two of the bacterial genes acquired by LGT appear to be important for activating and inactivating metronidazole, the best drug against these organisms.
- Professor, Microbiology, Boston University School of Medicine
- Graduate Faculty (Primary Mentor of Grad Students), Boston University School of Medicine, Graduate Medical Sciences
- Member, Bioinformatics Graduate Program, Boston University
- Harvard Medical School, MD
- Harvard Medical School, PhD
- Swarthmore College, BA
- Published on 5/16/2019
Magistrado-Coxen P, Aqeel Y, Lopez A, Haserick JR, Urbanowicz BR, Costello CE, Samuelson J. The most abundant cyst wall proteins of Acanthamoeba castellanii are lectins that bind cellulose and localize to distinct structures in developing and mature cyst walls. PLoS Negl Trop Dis. 2019 May; 13(5):e0007352. PMID: 31095564.
- Published on 2/18/2019
Bandini G, Albuquerque-Wendt A, Hegermann J, Samuelson J, Routier FH. Protein O- and C-Glycosylation pathways in Toxoplasma gondii and Plasmodium falciparum. Parasitology. 2019 Feb 18; 1-12. PMID: 30773146.
- Published on 12/11/2018
Bandini G, Leon DR, Hoppe CM, Zhang Y, Agop-Nersesian C, Shears MJ, Mahal LK, Routier FH, Costello CE, Samuelson J. O-Fucosylation of thrombospondin-like repeats is required for processing of microneme protein 2 and for efficient host cell invasion by Toxoplasma gondii tachyzoites. J Biol Chem. 2019 02 08; 294(6):1967-1983. PMID: 30538131.
- Published on 11/21/2018
Gas-Pascual E, Ichikawa HT, Sheikh MO, Serji MI, Deng B, Mandalasi M, Bandini G, Samuelson J, Wells L, West CM. CRISPR/Cas9 and glycomics tools for Toxoplasma glycobiology. J Biol Chem. 2019 01 25; 294(4):1104-1125. PMID: 30463938.
- Published on 10/18/2017
Dubey R, Harrison B, Dangoudoubiyam S, Bandini G, Cheng K, Kosber A, Agop-Nersesian C, Howe DK, Samuelson J, Ferguson DJP, Gubbels MJ. Differential Roles for Inner Membrane Complex Proteins across Toxoplasma gondii and Sarcocystis neurona Development. mSphere. 2017 Sep-Oct; 2(5). PMID: 29062899.
- Published on 8/8/2017
Haserick JR, Klein JA, Costello CE, Samuelson J. Cryptosporidium parvum vaccine candidates are incompletely modified with O-linked-N-acetylgalactosamine or contain N-terminal N-myristate and S-palmitate. PLoS One. 2017; 12(8):e0182395. PMID: 28792526.
- Published on 2/9/2017
Aqeel Y, Rodriguez R, Chatterjee A, Ingalls RR, Samuelson J. Killing of diverse eye pathogens (Acanthamoeba spp., Fusarium solani, and Chlamydia trachomatis) with alcohols. PLoS Negl Trop Dis. 2017 Feb; 11(2):e0005382. PMID: 28182670.
- Published on 2/8/2017
Haserick JR, Leon DR, Samuelson J, Costello CE. Asparagine-Linked Glycans of Cryptosporidium parvum Contain a Single Long Arm, Are Barely Processed in the Endoplasmic Reticulum (ER) or Golgi, and Show a Strong Bias for Sites with Threonine. Mol Cell Proteomics. 2017 Apr; 16(4 suppl 1):S42-S53. PMID: 28179475.
- Published on 11/16/2016
Sanz S, López-Gutiérrez B, Bandini G, Damerow S, Absalon S, Dinglasan RR, Samuelson J, Izquierdo L. The disruption of GDP-fucose de novo biosynthesis suggests the presence of a novel fucose-containing glycoconjugate in Plasmodium asexual blood stages. Sci Rep. 2016 11 16; 6:37230. PMID: 27849032.
- Published on 9/23/2016
Bandini G, Haserick JR, Motari E, Ouologuem DT, Lourido S, Roos DS, Costello CE, Robbins PW, Samuelson J. O-fucosylated glycoproteins form assemblies in close proximity to the nuclear pore complexes of Toxoplasma gondii. Proc Natl Acad Sci U S A. 2016 10 11; 113(41):11567-11572. PMID: 27663739.
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