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Leprosy – clues about the biochemistry of Mycobacterium leprae and its host-dependency from the genome

  • Paul R. Wheeler
Article

Abstract

Deletions and the appearance of pseudogenes in pathways of carbon source utilisation and energy metabolism best explain the host-dependency and failure to culture Mycobacterium leprae axenically. From the genome sequence it is possible to predict that acetate and galactose cannot be used as carbon sources, while pyruvate can only be catabolised. Glycerol, glucose, and fatty acids could be used for glycolysis, the pentose cycle and β-oxidation which are complete. Retrospective functional genomics – interpreting work before the completion of the genome project – supports the failure of M. leprae to use acetate as well as another prediction that metabolic flux from pyruvate to acetyl-CoA would be very low. However, the loss of a second icd gene (compared with M. tuberculosis), predicted to encode isocitrate dehydrogenase, did not diminish the specific activity of the enzyme. The genes for respiratory pathways are extremely limited, being present for oxidative phosphorylation as a result of electron transport only using FADH as an electron donor. In contrast, all the major biosynthetic pathways are complete except that M. leprae is a natural methionine auxotroph: this is predicted not to be attenuating, or explain host-dependency since methionine would be present in ‘rich’ culture media.

Leprosy Loss of paralogous genes in carbon metabolism Loss of paralogous genes in Mycobacterium leprae Microaerophilic niche for Mycobacterium leprae Muller's Ratchet Pseudogenes accumulation of in the Mycobacterium leprae genome Requirements for axenic culture of Mycobacterium leprae 

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© Kluwer Academic Publishers 2003

Authors and Affiliations

  • Paul R. Wheeler
    • 1
  1. 1.Tuberculosis Research Unit, Department of Bacterial Diseases, Veterinary Laboratories Agency (Weybridge)New HawUK;Tel.:

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