The long-term objective of our studies is to understand the ability of the pathogenetic human trichomonads to parasitize host cells and tissues in order to increase our knowledge of the chronic nature and pathobiochemistry of trichomoniasis. Our current research proposal is aimed at dissecting the nature of the highly specific recognition events between Trichomonas vaginalis and vaginal epithelial cells and basement membranes. This area of research is highly relevant as the ability to attach to host cells and tissues is the key to urogenital infection and pathogenesis. It is likely at this work will result in identification of adhesin-peptide virulence factors. The specific parasite molecules then are a basis for immunologic or pharmacologic disease intervention strategies. The research will be divided into four separate but related areas. Part I of our grant is aimed toward isolation and characterization of trichomonad surface proteins which are responsible for the receptor-ligand parasitism of epithelial cells. Part II builds upon our knowledge of T. vaginalis-host cell interactions and involves ascertaining the biological significance conferred upon T. vaginalis by selective recognition of extracellular matrix fibronectin. In Part III we propose to generate nospecific and monoclonal antibodies to the host epithelial cell- and fibronectin-binding proteins of T. vaginalis. These antibodies will be used for determining the specificity and structure-function properties of the interactions between host and parasite. Finally, antibodies will be used to screen established and future cDNA libraries as presented in Part IV. Recombinant genes and proteins will be important for further dissecting of the parasite-host recognition systems at the molecular level. This research utilizes cellular and molecular biological, biochemical, and immunological techniques and approaches to address an important aspect of the T. vaginalis: host relationship. It is likely that results from these studies will be useful for other pathogenic protozoan model systems where cytadherence is key to establishment and maintenance of infection.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI018768-10
Application #
2060770
Study Section
Tropical Medicine and Parasitology Study Section (TMP)
Project Start
1982-04-01
Project End
1995-11-30
Budget Start
1993-12-01
Budget End
1994-11-30
Support Year
10
Fiscal Year
1994
Total Cost
Indirect Cost
Name
University of Texas Health Science Center San Antonio
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
800772162
City
San Antonio
State
TX
Country
United States
Zip Code
78229
Engbring, J A; Alderete, J F (1998) Three genes encode distinct AP33 proteins involved in Trichomonas vaginalis cytoadherence. Mol Microbiol 28:305-13
Alderete, J F; Engbring, J; Lauriano, C M et al. (1998) Only two of the Trichomonas vaginalis triplet AP51 adhesins are regulated by iron. Microb Pathog 24:1-16
Provenzano, D; Khoshnan, A; Alderete, J F (1997) Involvement of dsRNA virus in the protein composition and growth kinetics of host Trichomonas vaginalis. Arch Virol 142:939-52
Engbring, J A; O'Brien, J L; Alderete, J F (1996) Trichomonas vaginalis adhesin proteins display molecular mimicry to metabolic enzymes. Adv Exp Med Biol 408:207-23
Alderete, J F; Provenzano, D; Lehker, M W (1995) Iron mediates Trichomonas vaginalis resistance to complement lysis. Microb Pathog 19:93-103
Provenzano, D; Alderete, J F (1995) Analysis of human immunoglobulin-degrading cysteine proteinases of Trichomonas vaginalis. Infect Immun 63:3388-95
Arroyo, R; Alderete, J F (1995) Two Trichomonas vaginalis surface proteinases bind to host epithelial cells and are related to levels of cytoadherence and cytotoxicity. Arch Med Res 26:279-85
Alderete, J F; Arroyo, R; Lehker, M W (1995) Analysis for adhesins and specific cytoadhesion of Trichomonas vaginalis. Methods Enzymol 253:407-14
Khoshnan, A; Alderete, J F (1995) Characterization of double-stranded RNA satellites associated with the Trichomonas vaginalis virus. J Virol 69:6892-7
Alderete, J F; O'Brien, J L; Arroyo, R et al. (1995) Cloning and molecular characterization of two genes encoding adhesion proteins involved in Trichomonas vaginalis cytoadherence. Mol Microbiol 17:69-83

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