The purpose of this completely revamped resubmission is the identification and implementation of new antigens for the diagnosis and epidemiological monitoring of leprosy and is based on the just-sequenced contiguous M. leprae genome, on the investigators' singular access to the bacillus, and driven by the extraordinary epidemiological conundrum of a convergence of falling prevalence and rising incidence. The other hypothesis-driven thrust is that a defective genotype must be reflected in a truncated phenotype, the definition of which will also provide knowledge and tools to help explain the peculiarities of leprosy, such as obligate intracellularism, characteristic cell tropism and reactions. S. Cole (Institut Pasteur) will complete the analysis and annotation of the genome and generate databases to provide the means for a two-laboratory effort (L'Institut Pasteur; CSU) to define the transcriptome, polymorphism within the infectious agent, and the entire simplified proteome through cloning of targeted genes and definition of the full array of in vivo expressed proteins. CSU will apply the genome and the structural knowledge of mycobacteria to define the simplified secondary gene products (LepLAM; LM; new extracellular lipids; peptidoglycan; etc.). CSU, Fio-Cruz (C. Pessolani), and Yonsei University (S.-N. Cho) will combine to test new products in guinea pigs for DTH responses, against PBMC's of leprosy patients for appropriate T-cell reactivity, and against sera for antibody responses, with a view to advancing the new skin antigen initiative and providing new blood assays for early diagnosis and identification of a t risk populations.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI047197-04
Application #
6743104
Study Section
Bacteriology and Mycology Subcommittee 2 (BM)
Program Officer
Sizemore, Christine F
Project Start
2001-06-15
Project End
2006-04-30
Budget Start
2004-05-01
Budget End
2005-04-30
Support Year
4
Fiscal Year
2004
Total Cost
$386,836
Indirect Cost
Name
Colorado State University-Fort Collins
Department
Microbiology/Immun/Virology
Type
Schools of Veterinary Medicine
DUNS #
785979618
City
Fort Collins
State
CO
Country
United States
Zip Code
80523
Kim, Hee Jin; Prithiviraj, Kalyani; Groathouse, Nathan et al. (2013) Gene expression profile and immunological evaluation of unique hypothetical unknown proteins of Mycobacterium leprae by using quantitative real-time PCR. Clin Vaccine Immunol 20:181-90
Fontes, Amanda Nogueira Brum; Gomes, Harrison Magdinier; Araujo, Marcelo Ivens de et al. (2012) Genotyping of Mycobacterium leprae present on Ziehl-Neelsen-stained microscopic slides and in skin biopsy samples from leprosy patients in different geographic regions of Brazil. Mem Inst Oswaldo Cruz 107 Suppl 1:143-9
Torrelles, Jordi B; Sieling, Peter A; Zhang, Nannan et al. (2012) Isolation of a distinct Mycobacterium tuberculosis mannose-capped lipoarabinomannan isoform responsible for recognition by CD1b-restricted T cells. Glycobiology 22:1118-27
Martins, Marcia V S B; GuimarĂ£es, Marjorie M da S; Spencer, John S et al. (2012) Pathogen-specific epitopes as epidemiological tools for defining the magnitude of Mycobacterium leprae transmission in areas endemic for leprosy. PLoS Negl Trop Dis 6:e1616
McShane, Helen; Jacobs, William R; Fine, Paul E et al. (2012) BCG: myths, realities, and the need for alternative vaccine strategies. Tuberculosis (Edinb) 92:283-8
Spencer, John S; Duthie, Malcolm S; Geluk, Annemieke et al. (2012) Identification of serological biomarkers of infection, disease progression and treatment efficacy for leprosy. Mem Inst Oswaldo Cruz 107 Suppl 1:79-89
Truman, Richard W; Singh, Pushpendra; Sharma, Rahul et al. (2011) Probable zoonotic leprosy in the southern United States. N Engl J Med 364:1626-33
Spencer, John S; Kim, Hee Jin; Wheat, William H et al. (2011) Analysis of antibody responses to Mycobacterium leprae phenolic glycolipid I, lipoarabinomannan, and recombinant proteins to define disease subtype-specific antigenic profiles in leprosy. Clin Vaccine Immunol 18:260-7
Singh, Pushpendra; Cole, Stewart T (2011) Mycobacterium leprae: genes, pseudogenes and genetic diversity. Future Microbiol 6:57-71
Geluk, Annemieke; van den Eeden, Susan J F; Dijkman, Karin et al. (2011) ML1419c peptide immunization induces Mycobacterium leprae-specific HLA-A*0201-restricted CTL in vivo with potential to kill live mycobacteria. J Immunol 187:1393-402

Showing the most recent 10 out of 35 publications