RESUMEN
The genome of Mycobacterium leprae, the etiologic agent of leprosy, has been sequenced and annotated revealing a genome in apparent disarray and in stark contrast to the genome of the related human pathogen, M. tuberculosis. With less than 50% coding capacity of a 3.3-Mb genome and 1,116 pseudogenes, the remaining genes help define the minimal gene set necessary for in vivo survival of this mycobacterial pathogen as well as genes potentially required for infection and pathogenesis seen in leprosy. To identify genes transcribed during infection, we surveyed gene transcripts from M. leprae growing in athymic nude mice using reverse transcriptase-polymerase chain reaction (RT-PCR) and cross-species DNA microarray technologies. Transcripts were detected for 221 open reading frames, which included genes involved in DNA replication, cell division, SecA-dependent protein secretion, energy production, intermediary metabolism, iron transport and storage and genes associated with virulence. These results suggest that M. leprae actively catabolizes fatty acids for energy, produces a large number of secretory proteins, utilizes the full array of sigma factors available, produces several proteins involved in iron transport, storage and regulation in the absence of recognizable genes encoding iron scavengers and transcribes several genes associated with virulence in M. tuberculosis. When transcript levels of 9 of these genes were compared from M. leprae derived from lesions of multibacillary leprosy patients and infected nude mouse foot pad tissue using quantitative real-time RT-PCR, gene transcript levels were comparable for all but one of these genes, supporting the continued use of the foot pad infection model for M. leprae gene expression profiling. Identifying genes associated with growth and survival during infection should lead to a more comprehensive understanding of the ability of M. leprae to cause disease.
Asunto(s)
Biología Computacional/métodos , Regulación Bacteriana de la Expresión Génica/genética , Genoma Bacteriano , Lepra/genética , Mycobacterium leprae/genética , Animales , Perfilación de la Expresión Génica , Regulación Bacteriana de la Expresión Génica/fisiología , Humanos , Lepra/metabolismo , Ratones , Mycobacterium leprae/metabolismo , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
Mycobacterium bovis is the causative agent of tuberculosis in a range of animal species and man, with worldwide annual losses to agriculture of $3 billion. The human burden of tuberculosis caused by the bovine tubercle bacillus is still largely unknown. M. bovis was also the progenitor for the M. bovis bacillus Calmette-Guérin vaccine strain, the most widely used human vaccine. Here we describe the 4,345,492-bp genome sequence of M. bovis AF2122/97 and its comparison with the genomes of Mycobacterium tuberculosis and Mycobacterium leprae. Strikingly, the genome sequence of M. bovis is >99.95% identical to that of M. tuberculosis, but deletion of genetic information has led to a reduced genome size. Comparison with M. leprae reveals a number of common gene losses, suggesting the removal of functional redundancy. Cell wall components and secreted proteins show the greatest variation, indicating their potential role in host-bacillus interactions or immune evasion. Furthermore, there are no genes unique to M. bovis, implying that differential gene expression may be the key to the host tropisms of human and bovine bacilli. The genome sequence therefore offers major insight on the evolution, host preference, and pathobiology of M. bovis.
Asunto(s)
Genoma Bacteriano , Modelos Biológicos , Modelos Genéticos , Datos de Secuencia Molecular , Mycobacterium bovis/genética , Mycobacterium tuberculosis/genética , Análisis de Secuencia de ADN , Especificidad de la EspecieRESUMEN
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