Toxoplasma gondii, microsporidiosis, stage differentiation, polar tube structure and function

Toxoplasmosis: Toxoplasma gondii is a ubiquitous Apicomplexan protozoan parasite that infects humans, mammals and birds.  Despite recent progress in understanding the biology of the rapidly replicating form (tachyzoite), very little is known about the cyst form (bradyzoite). The bradyzoite stage plays a critical role in maintenance of latent infection, the relapse of infections and the development of chronic neurologcial disease.  Our research is focused on the identification of cyst wall  (bradyzoite) proteins and how they function.   

Microsporidiosis: The phylum Microspora consists of organisms collectively known as microsporidia, that are "emerging" human and veterinary pathogens.  A microsporidian-specific organelle, the polar tube, is involved in invasion. While the description of the polar tube as a unique microsporidian structure occurred over 100 years ago, the biochemical components of this structure and the mechanism of its formation during invasion remain to be definitively determined.  The laboratory is focused on projects invovling the: (1) characterization of the structure and composition of the polar tube and spore wall, and (2) the identificiation of therapeutic targets for the treatment of microsporidiosis. 

Mayoral J, Guevara RB, Rivera-Cuevas Y, Tu V, Tomita T, Romano JD, Gunther-Cummins L, Sidoli S, Coppens I, Carruthers VB, Weiss LM.  Dense Granule Protein GRA64 interacts with host cell ESCRT proteins during Toxoplasma gondii infection.mBio. 2022 Jun 22:e0144222. doi: 10.1128/mbio.01442-22.

Tomita T, Mukhopadhyay D, Han B, Yakubu R, Tu V, Mayoral J, Sugi T, Ma Y, Saeij JPJ, Weiss LM. Toxoplasma gondii matrix antigen 1 is a secreted immunomodulatory effector. mBio. 2021 May 18;12(3):e00603-21. 

Flores J, Takvorian PM, Weiss LM, Cali A, Gao N. Human microsporidian pathogen Encephalitozoon intestinalis impinges on enterocyte membrane trafficking and signaling. J Cell Sci. 2021 Feb 15:jcs.253757. doi: 10.1242/jcs.253757.

Mayoral J, Tomita T, Tu V, Aguilan JT, Sidoli S, Weiss LM. Toxoplasma gondii PPM3C, a secreted protein phosphatase, affects parasitophorous vacuole effector export. PLoS Pathog. 2020 Dec 28;16(12):e1008771. doi: 10.1371/journal.ppat.1008771. 

Mayoral J, Shamamian P Jr, Weiss LM. In Vitro Characterization of protein effector export in the bradyzoite stage of Toxoplasma gondii.  mBio. 2020 Mar 10;11(2). pii: e00046-20. doi: 10.1128/mBio.00046-20. PMID: 32156805

Tu V, Tomita T, Sugi T, Mayoral J, Han B, Yakubu RR, Williams T, Horta A, Ma Y, Weiss LM. The Toxoplasma gondii cyst wall interactome. mBio. 2020 Feb 4;11(1). pii: e02699-19. doi: 10.1128/mBio.02699-19.PMID: 32019789

Tu V, Mayoral J, Yakubu RR, Tomita T, Sugi T, Han B, Williams T, Ma Y, Weiss LM.MAG2, a Toxoplasma gondii bradyzoite stage-specific cyst matrix protein. mSphere. 2020 Feb 19;5(1). pii: e00100-20. doi:10.1128/mSphere.00100-20.PMID: 32075884

Han B, Ma Y, Tu V, Tomita T, Mayoral J, Williams T, Horta A, Huang H, Weiss LM Microsporidia interact with host cell mitochondria via voltage-dependent anion channels using sporoplasm Surface Protein 1. mBio. 2019 Aug 20;10(4). pii: e01944-19. doi: 10.1128/mBio.01944-19. PMID: 31431557 PMC6703431

Takvorian PM, Han B, Cali A, Rice WJ, Gunther L, Macaluso F, Weiss LM. An ultrastructural study of the extruded polar tube of Anncaliia algerae (Microsporidia). J Eukaryot Microbiol. 2019 Jul 22. doi: 10.1111/jeu.12751. PMID: 31332877

Tomita T, Wang H, Wu P, Weiss LM.Stage-specific and selective delivery of caged azidosugars into the intracellular parasite Toxoplasma gondii by using an esterase-ester pair technique.  mSphere. 2019 May 29;4(3). pii: e00142-19. doi: 10.1128/mSphere.00142-19. PMID: 31142619

Tu V, Mayoral J, Sugi T, Tomita T, Han B, Ma YF, Weiss LM. Enrichment and proteomic characterization of the cyst wall from in vitro Toxoplasma gondii cysts. mBio. 2019 Apr 30;10(2). pii: e00469-19. doi: 10.1128/mBio.00469-19. PMID: 31040239

Sugi T, Tu V, Ma Y, Tomita T, Weiss LM. Toxoplasma gondii requires glycogen phosphorylase for balancing amylopectin storage and for efficient production of brain cysts. mBio. 2017 Aug 29;8(4). pii: e01289-17. doi: 10.1128/mBio.01289-17.PMID: 28851850 PMC5574715

Yakubu RR, Silmon de Monerri NC, Nieves E, Kim K, Weiss LM. Comparative Monomethylarginine proteomics suggests that protein arginine methyltransferase 1 (PRMT1) is a significant contributor to arginine monomethylation in Toxoplasma gondii. Mol Cell Proteomics. 2017 Apr;16(4):567-580. doi: 10.1074/mcp.M117.066951. Epub 2017 Jan 31.PMID: 28143887

Han B, Polonais V, Sugi T, Yakubu R, Takvorian PM, Cali A, Maier K, Long M, Levy M, Tanowitz HB, Pan G, Delbac F, Zhou Z, Weiss LM. The role of microsporidian polar tube protein 4 (PTP4) in host cell infection. PLoS Pathog. 2017 Apr 20;13(4):e1006341. doi: 10.1371/journal.ppat.1006341. eCollection 2017 Apr. PMID: 28426751

Sugi T, Ma YF, Tomita T, Murakoshi F, Eaton MS, Yakubu R, Han B, Tu V, Kato K, Kawazu S, Gupta N, Suvorova ES, White MW, Kim K, Weiss LM. Toxoplasma gondii cyclic AMP-dependent protein kinase subunit 3 is involved in the switch from tachyzoite to bradyzoite development. mBio. 2016 May 31;7(3). pii: e00755-16. doi: 10.1128/mBio.00755-16. PMID: 27247232 PMCID: PMC4895117

El Bissati K, Suvorova ES, Xiao H, Lucas O, Upadhya R, Yan Fen Ma YF, Hogue Angeletti R, White MW, Weiss LM, Kim K Toxoplasma gondii arginine methyltransferase 1 (PRMT1) regulates centrosome dynamics during tachyzoite cell division. mBio. 2016 Feb 2;7(1):e02094-15. doi: 10.1128/mBio.02094-15. PMID: 26838719 PMCID: PMC4742710

Silmon de Monerri NC, Yakubu RR, Chen AL, Bradley PJ, Nieves E, Weiss LM, Kim K. The Ubiquitin proteome of Toxoplasma gondii reveals roles for protein ubiquitination in cell-cycle transitions. Cell Host Microbe. 2015 Nov 11;18(5):621-33. doi: 10.1016/j.chom.2015.10.014. PMID: 26567513

Tomita T, Bzik DJ, Ma YF, Fox BA, Markillie LM, Taylor RC, Kim K, Weiss LM.The Toxoplasma gondii cyst wall protein CST1 is critical for cyst wall integrity and promotes bradyzoite persistence.  PLoS Pathog. 2013 Dec;9(12):e1003823. doi: 10.1371/journal.ppat.1003823. PMID:24385904

Morada M, Lee S, Gunther-Cummins L, Weiss LM, Widmer G, Tzipori S, Yarlett N. Continuous culture of Cryptosporidium parvum using hollow fiber technology. Int J Parasitol. 2015 Sep 2. pii: S0020-7519(15)00220-9. doi: 10.1016/j.ijpara.2015.07.006. PMID: 26341006

Ma Y, Weiss LM, Huang H. Inducible suicide vector systems for Trypanosoma cruzi. Microbes Infect. 2015 Jun;17(6):440-50. doi: 10.1016/j.micinf.2015.04.003. Epub 2015 Apr 18. PMID: 25899945

Nardelli SC, Che FY, Silmon de Monerri NC, Xiao H, Nieves E, Madrid-Aliste C, Angel SO, Sullivan WJ Jr, Angeletti RH, Kim K, Weiss LM.  The Histone Code of Toxoplasma gondii Comprises Conserved and Unique Posttranslational Modifications. mBio. 2013 Dec 10;4(6). doi:pii: e00922-13. 10.1128/mBio.00922-13. PMID:24327343

Pombert JF,Selman M,Burki F,Bardell FT,Farinelli L,Solter LF,Whitman DW,Weiss LM, Corradi N, Keeling PJ.   Gain and loss of multiple functionally related, horizontally transferred genes in the reduced genomes of two microsporidian parasites.  Proc Natl Acad Sci U S A. 2012 Jul 31;109(31):12638-43. Epub 2012 Jul 16. PMID:22802648

Ghosh K, Nieves E, Keeling P, CaliA, Weiss LM. A new vesicular compartment in Encephalitozoon cuniculi. Microbes Infect. 2012 Apr;14(4):324-8. PMID:22166342

Ghosh K, Nieves E, Keeling P, Pombert JF, CaliA, Weiss LM. A branching network of proteinaceous filaments within the parasitophorous vacuole of Encephalitozoon cuniculi and Encephalitozoon hellem. Infect Immun. 2011 Jan 10. PMID: 21220485

Bouzahzah B, Nagajyothi F, Ghosh K, Takvorian PM, CaliA, Tanowitz HB, Weiss LM. Interactions of Encephalitozoon cuniculi polar tube proteins. Infect Immun. 2010 Jun;78(6):2745-53. Epub 2010 Mar 22. PMID: 20308291

Alvarado JJ, Nemkal A, Sauder JM, Russell M, Akiyoshi DE, Shi W, Almo SC, Weiss LM. Structure of a microsporidian methionine aminopeptidase type 2 complexed with fumagillin and TNP-470. Mol Biochem Parasitol. 2009 Aug 4. PMID: 19660503

BOOKS

Weiss LM and Kim K (eds.) Toxoplasma gondii the model Apicomplexan: Methods and Applications,  Elsevier Press (Academic Press), 3rd edition, 2020.

Weiss LM and Reinke AW (eds.) Microsporidia: Current Advances in Biology, Springer, 2022.

Weiss LM and Becnel JJ (eds.) Microsporidia: Pathogens of Opportunity,  Wiley-Blackwell, 2014.