02879nas a2200361   4500000000100000008004100001260000900042653001200051653002600063653003000089653004200119653002200161653001100183653001200194653000900206653002500215653003100240653005200271100001600323700001400339700001400353700001400367700001200381700001500393700001400408700001300422245008600435300001000521490000600531050001800537520194800555022001402503       2004                            d  c200410aAnimals10aComputational Biology10aGene Expression Profiling10aGene Expression Regulation, Bacterial10aGenome, Bacterial10aHumans10aleprosy10aMice10aMycobacterium leprae10aMycobacterium tuberculosis10aReverse Transcriptase Polymerase Chain Reaction1 aWilliams DL1 aTorrero M1 aWheeler P1 aTruman RW1 aYoder M1 aMorrison N1 aBishai WR1 aGillis T00aBiological implications of Mycobacterium leprae gene expression during infection.  a58-720 v8  aWILLIAMS 20043 a<p>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.</p>  a1464-1801