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1.
Microbes Infect ; 8(8): 2270-6, 2006 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-16797206

RESUMO

In addition to multidrug therapy, elimination of leprosy requires improved diagnostic methods. Using a comparative genomics approach, 17 potential protein antigens (MLP) that are restricted to Mycobacterium leprae, or of limited distribution, were produced and tested for antigen-specific immune responses on leprosy patients, healthy contacts of leprosy patients, and tuberculosis patients in Mali and Bangladesh, as well as on non-endemic controls. T-cell antigenicity of MLP was confirmed by IFN-gamma production in whole-blood assays with the highest responses observed in paucibacillary leprosy patients and healthy contacts. Four MLP behaved well in both countries and induced significantly different responses between the study groups. Peptides carrying T cell epitopes from one of the antigens gave promising results in restimulation assays in mice and immune responses were not influenced by prior exposure to BCG or environmental mycobacteria. This study provides the immunological framework for the development of a specific, peptide-based immunodiagnostic test for leprosy.


Assuntos
Testes Imunológicos/métodos , Hanseníase/diagnóstico , Mycobacterium leprae/imunologia , Sequência de Aminoácidos , Animais , Anticorpos Antibacterianos/biossíntese , Antígenos de Bactérias/imunologia , Células Cultivadas , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Interferon gama/biossíntese , Hanseníase/imunologia , Leucócitos Mononucleares/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Dados de Sequência Molecular , Mycobacterium leprae/isolamento & purificação , Peptídeos/imunologia , Linfócitos T/imunologia
2.
Infect Immun ; 74(1): 175-82, 2006 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16368971

RESUMO

Leprosy is an infectious, neurodegenerative disease of humans caused by Mycobacterium leprae. Despite effective control programs, the incidence of leprosy remains stubbornly high, suggesting that transmission may be more common than expected. The rationale of this work was to use bioinformatics and comparative genomics to identify potentially antigenic proteins for diagnostic purposes. This approach defined three classes of proteins: those restricted to M. leprae (class I), those present in M. leprae with orthologues in other organisms besides mycobacteria (class II), and exported or surface-exposed proteins (class III). Twelve genes (two class I, four class II, and six class III proteins) were cloned in Escherichia coli, and their protein products were purified. Six of these proteins were detected in cell extracts of M. leprae by immunoblotting. The immunogenicity of each recombinant protein was then investigated in leprosy patients by measuring the reactivity of circulating antibody and gamma interferon (IFN-gamma) responses in T-cell restimulation assays. Several class II and class III proteins were recognized by circulating antibodies. Importantly, most class II proteins elicited IFN-gamma responses that were significantly stronger than those produced by previously identified antigens. Among them, two class II proteins, ML0308 and ML2498, showed marked humoral and cellular immunogenicity, therefore providing promising candidates for the diagnosis of both tuberculoid and lepromatous forms of leprosy.


Assuntos
Antígenos de Bactérias/imunologia , Genoma Bacteriano , Hanseníase/diagnóstico , Mycobacterium leprae/imunologia , Sequência de Aminoácidos , Anticorpos Antibacterianos/biossíntese , Anticorpos Antibacterianos/sangue , Antígenos de Bactérias/biossíntese , Antígenos de Bactérias/genética , Biologia Computacional , Genes Bacterianos , Humanos , Interferon gama/metabolismo , Hanseníase/sangue , Hanseníase/imunologia , Hanseníase/metabolismo , Dados de Sequência Molecular
3.
Science ; 308(5724): 1040-2, 2005 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-15894530

RESUMO

Leprosy, a chronic human disease with potentially debilitating neurological consequences, results from infection with Mycobacterium leprae. This unculturable pathogen has undergone extensive reductive evolution, with half of its genome now occupied by pseudogenes. Using comparative genomics, we demonstrated that all extant cases of leprosy are attributable to a single clone whose dissemination worldwide can be retraced from analysis of very rare single-nucleotide polymorphisms. The disease seems to have originated in Eastern Africa or the Near East and spread with successive human migrations. Europeans or North Africans introduced leprosy into West Africa and the Americas within the past 500 years.


Assuntos
Emigração e Imigração , Hanseníase/história , Mycobacterium leprae/genética , África/epidemiologia , América/epidemiologia , Ásia/epidemiologia , Evolução Biológica , Europa (Continente)/epidemiologia , Genes Bacterianos , Genoma Bacteriano , História do Século XVIII , História do Século XIX , História Antiga , História Medieval , Humanos , Sequências Repetitivas Dispersas , Hanseníase/epidemiologia , Hanseníase/microbiologia , Hanseníase/transmissão , Repetições Minissatélites , Mycobacterium leprae/classificação , Análise de Sequência com Séries de Oligonucleotídeos , Polimorfismo de Nucleotídeo Único , Dinâmica Populacional , Pseudogenes , Análise de Sequência de DNA
4.
s.l; s.n; 2005. 3 p. tab, graf, mapas.
Não convencional em Inglês | Sec. Est. Saúde SP, HANSEN, Hanseníase, SESSP-ILSLPROD, Sec. Est. Saúde SP, SESSP-ILSLACERVO, Sec. Est. Saúde SP | ID: biblio-1097746

RESUMO

Leprosy, a chronic human disease with potentially debilitating neurological consequences, results from infection with Mycobacterium leprae. This unculturable pathogen has undergone extensive reductive evolution, with half of its genome now occupied by pseudogenes. Using comparative genomics, we demonstrated that all extant cases of leprosy are attributable to a single clone whose dissemination worldwide can be retraced from analysis of very rare single-nucleotide polymorphisms. The disease seems to have originated in Eastern Africa or the Near East and spread with successive human migrations. Europeans or North Africans introduced leprosy into West Africa and the Americas within the past 500 years.


Assuntos
Humanos , História Antiga , História Medieval , História do Século XVIII , História do Século XIX , Ásia/epidemiologia , América/epidemiologia , Pseudogenes , Genoma Bacteriano , Análise de Sequência com Séries de Oligonucleotídeos , Polimorfismo de Nucleotídeo Único , África/epidemiologia , Emigração e Imigração , Europa (Continente)/epidemiologia , Genes Bacterianos , Hanseníase/história , Hanseníase/microbiologia , Hanseníase/transmissão , Hanseníase/epidemiologia , Mycobacterium leprae/classificação , Mycobacterium leprae/genética
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