This research proposal is focused on the significance of multiple gene copies for protein P1 with regards to the observed biological role of P1 as an integral adhesin necessary for cytadherence of Mycoplasma pneumoniae to human respiratory epithelium. Emphasis is place on defining at the molecular level the epitopes within P1 necessary for cytadherence and detecting antigenic or biological alterations in these epitopes in wild-type, mutant and clinical isolate populations. The definition of functional epitopes within P1 and the identification of unique-sequences form P1-related gene fragments will be used to explore the factors which affects the expression and biological role of adhesin P1 in virulence. Technologies to be used range from cloning and sequencing of P1 and P1-related gene sequences to analysis of mRNA transcripts and development of expression systems for M. pneumoniae proteins. In addition, synthetic peptides will be examined from vaccine and serodiagnostic value and will assist in characterization of host receptors. We expect that other activities of P1 will be uncovered in addition to those related to cytadherence. It is expected that information obtained from this study will result in a significantly better molecular understanding of the virulence process of Mycoplasma pneumoniae. This understanding will ultimately lead to interventions for the prevention of pneumonia cause by M. pneumoniae and related infections. More generally, these studies will further the understanding of the role of gene conversion in the alteration of protein domains with biofunctional significance.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
1R01AI027873-01
Application #
3142167
Study Section
Bacteriology and Mycology Subcommittee 1 (BM)
Project Start
1989-09-01
Project End
1994-08-31
Budget Start
1989-09-01
Budget End
1990-08-31
Support Year
1
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of Texas Health Science Center San Antonio
Department
Type
Overall Medical
DUNS #
800772162
City
San Antonio
State
TX
Country
United States
Zip Code
78229
Baseman, J B; Tully, J G (1997) Mycoplasmas: sophisticated, reemerging, and burdened by their notoriety. Emerg Infect Dis 3:21-32
Dallo, S F; Lazzell, A L; Chavoya, A et al. (1996) Biofunctional domains of the Mycoplasma pneumoniae P30 adhesin. Infect Immun 64:2595-601
Reddy, S P; Rasmussen, W G; Baseman, J B (1996) Isolation and characterization of transposon Tn4001-generated, cytadherence-deficient transformants of Mycoplasma pneumoniae and Mycoplasma genitalium. FEMS Immunol Med Microbiol 15:199-211
Giron, J A; Lange, M; Baseman, J B (1996) Adherence, fibronectin binding, and induction of cytoskeleton reorganization in cultured human cells by Mycoplasma penetrans. Infect Immun 64:197-208
Reddy, S P; Rasmussen, W G; Baseman, J B (1996) Correlations between Mycoplasma pneumoniae sensitivity to cyclosporin A and cyclophilin-mediated regulation of mycoplasma cytadherence. Microb Pathog 20:155-69
Baseman, J B; Reddy, S P; Dallo, S F (1996) Interplay between mycoplasma surface proteins, airway cells, and the protean manifestations of mycoplasma-mediated human infections. Am J Respir Crit Care Med 154:S137-44
Reddy, S P; Rasmussen, W G; Baseman, J B (1995) Molecular cloning and characterization of an adherence-related operon of Mycoplasma genitalium. J Bacteriol 177:5943-51
Su, C J; Dallo, S F; Chavoya, A et al. (1993) Possible origin of sequence divergence in the P1 cytadhesin gene of Mycoplasma pneumoniae. Infect Immun 61:816-22
Mernaugh, G R; Dallo, S F; Holt, S C et al. (1993) Properties of adhering and nonadhering populations of Mycoplasma genitalium. Clin Infect Dis 17 Suppl 1:S69-78
Su, C J; Dallo, S F; Alderman, H et al. (1991) Distinctions in DNA and protein profiles among clinical isolates of Mycoplasma pneumoniae. J Gen Microbiol 137:2727-32

Showing the most recent 10 out of 12 publications