The microsporidia are """"""""emerging"""""""" human and veterinary pathogens that cause disease in both immunocompromized and immunocompetent hosts. Our efforts are directed at understanding the invasion mechanism of these organisms involving the polar tube and its associated structures which form an organelle critical for cell invasion. The polar tube serves as a vehicle for transmission of infection by piercing an adjacent host cell inoculating the sporoplasm directly into that cell. The biochemical components of this structure and the mechanism of its formation during invasion remain to be definitively determined. Study of the composition, formation and function of this organelle during germination and invasion should provide a basis for the development of new strategies for control of these important parasitic protists. We plan to use a proteomics (mass spectrometry) approach to the characterization of the proteins of the polar tube (PTPs) and spore wall (SWPs) of the microsporidia. Encephalitozoon cuniculi, a human pathogenic microsporidia, will be used for these studies as the availability of its complete genome facilitates this proteomic approach. Recombination cloning will be used to express and characterize the identified proteins as this will allow high throughput expression analysis. The molecular interaction(s) of PTP1 with itself and with other PTPs will be evaluated using yeast two hybrid and GST pull- down techniques. Our characterization of these structures at the molecular level will be complemented by ultrastructural studies investigating the development and location of PTPs and SWPs during morphogenesis and eversion of the polar tube. Cryoelectron microscopy and EM tomography will provide insights into the 3D structure of the polar tube and spore wall during eversion, providing answers to fundamental questions on the organism of these structures that have not been resolved by traditional EM. For example, our observations suggest that the polar tube may be extracellular in the spore. We believe that the information gained by delineating, in detail, the function and components of the polar tube will eventually lead to novel therapeutic interventions that could limit or interdict the transmission of these emerging pathogens.

Public Health Relevance

. These are new pathogens for which there are limited effective drugs. Studies of how these organisms cause infection should result in the development of new therapeutic agents.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI031788-19
Application #
7771729
Study Section
AIDS-associated Opportunistic Infections and Cancer Study Section (AOIC)
Program Officer
Duncan, Rory A
Project Start
1992-04-01
Project End
2012-03-31
Budget Start
2010-04-01
Budget End
2011-03-31
Support Year
19
Fiscal Year
2010
Total Cost
$394,737
Indirect Cost
Name
Albert Einstein College of Medicine
Department
Pathology
Type
Schools of Medicine
DUNS #
110521739
City
Bronx
State
NY
Country
United States
Zip Code
10461
Han, Bing; Weiss, Louis M (2018) Therapeutic targets for the treatment of microsporidiosis in humans. Expert Opin Ther Targets 22:903-915
Yakubu, Rama R; Weiss, Louis M; Silmon de Monerri, Natalie C (2018) Post-translational modifications as key regulators of apicomplexan biology: insights from proteome-wide studies. Mol Microbiol 107:1-23
Santiana, Marianita; Pau, Cyrilla; Takvorian, Peter M et al. (2015) Analysis of the beta-tubulin gene and morphological changes of the microsporidium Anncaliia algerae both suggest albendazole sensitivity. J Eukaryot Microbiol 62:60-8
Pombert, Jean-François; Xu, Jinshan; Smith, David R et al. (2013) Complete genome sequences from three genetically distinct strains reveal high intraspecies genetic diversity in the microsporidian Encephalitozoon cuniculi. Eukaryot Cell 12:503-11
Jelicks, Linda A; Lisanti, Michael P; Machado, Fabiana S et al. (2013) Imaging of small-animal models of infectious diseases. Am J Pathol 182:296-304
Selman, Mohammed; Sak, Bohumil; Kvac, Martin et al. (2013) Extremely reduced levels of heterozygosity in the vertebrate pathogen Encephalitozoon cuniculi. Eukaryot Cell 12:496-502
Takvorian, Peter M; Buttle, Karolyn F; Mankus, David et al. (2013) The multilayered interlaced network (MIN) in the sporoplasm of the microsporidium Anncaliia algerae is derived from Golgi. J Eukaryot Microbiol 60:166-78
Weiss, Louis M; Cushion, Melanie T; Didier, Elizabeth et al. (2013) The 12th International Workshops on Opportunistic Protists (IWOP-12). J Eukaryot Microbiol 60:298-308
Pombert, Jean-François; Selman, Mohammed; Burki, Fabien et al. (2012) 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 109:12638-43
Zencheck, Wendy D; Xiao, Hui; Weiss, Louis M (2012) Lysine post-translational modifications and the cytoskeleton. Essays Biochem 52:135-45

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