01828nas a2200241 4500000000100000008004100001260000900042653002700051653001200078653001900090653001100109653001100120653001200131653002500143653001300168653002700181100001400208245009100222300001000313490000700323520124200330022001401572 2002 d c200210aChromosomes, Bacterial10aCosmids10aDNA, Bacterial10aGenome10aHumans10aleprosy10aMycobacterium leprae10aPlasmids10aSequence Analysis, DNA1 aHonoré N00a[The Mycobacterium leprae genome: from sequence analysis to therapeutic implications]. a473-90 v623 a

The genome of Mycobacterium leprae, the causative agent of leprosy, was analyzed by rapid sequencing of cosmids and plasmids prepared from DNA isolated from one patient's strain. Results showed that the bacillus possesses a single circular chromosome that differs from other known mycobacterium chromosomes with regard to size (3.2 Mb) and G + C content (57.8%). Computer analysis demonstrated that only half of the sequence contains protein-coding genes. The other half contains pseudogenes and non-coding sequences. These findings indicate that M. leprae has undergone a major reductive evolution leaving a minimal set of functional genes for survival. Study of the coding region of the sequence provides evidence accounting for the particular pathogenic properties of M. leprae which is an obligate intracellular parasite. Disappearance of numerous enzymatic pathways in comparison with M. tuberculosis, an intracellular pathogen comparable to M. leprae, could explain the differences observed between the two organisms. Genomic analysis of the leprosy bacillus also provided insight into the molecular basis for resistance to various antibiotics and allowed identification of several potential targets for new drug treatments.

 a0025-682X