The genome of Mycobacterium leprae: a minimal mycobacterial gene set

Abstract

Comparison of the recently sequenced genome of the leprosy-causing pathogen Mycobacterium leprae with other mycobacterial genomes reveals a drastic gene reduction and decay in M. leprae affecting many metabolic areas, exemplified by the retention of a minimal set of genes required for cell-wall biosynthesis.

Box 1

A list of abbreviations used in the glycoconjugate and sugar names

Figure 1

The extent of gene reduction and decay in the genome of M. leprae. (a) The percentage of the total potential open reading frames assigned to major cellular functions are shown. (b) Each category has been sub-classified and the number of putative functional genes in M. leprae (after eliminating the pseudogenes) for each subclass are indicated by bold numbers, followed by the corresponding number in M. tuberculosis. The data were obtained from the databases of the M. leprae and M. tuberculosis genome projects [2,4] as annotated by Cole et al. [1,3].

Figure 2

A schematic model of the cell envelope of M. leprae. The plasma membrane is covered by a cell-wall core made of peptidoglycan (chains of alternating GlcNAc and MurNGly, linked by peptide crossbridges) covalently linked to the galactan by a linker unit (-P-GlcNAc-Rha-) of arabinogalactan. Three branched chains of arabinan are in turn linked to the galactan. The peptidoglycan-arabinogalactan layer forms the electron-dense zone. Mycolic acids are linked to the termini of the arabinan chains to form the inner leaflet of a pseudo lipid bilayer. An outer leaflet is formed by the mycolic acids of TMM and mycocerosoic acids of PDIMs and PGLs as indicated. The pseudo-bilayer forms the electron-transparent zone. A capsule presumably composed largely of PGLs and other molecules such as PDIMs, PIMs and phospholipids surrounds the bacterium. Lipoglycans such as PIMs, LM and LAM, known to be anchored in the plasma membrane, are also found in the capsular layer as shown. Abbreviations are as used in the text and Box 1.

Figure 3

Genetic organization of the putative AG biosynthetic cluster in M. tuberculosis [23] and identification of a similar cluster in M. leprae and C. diphtheriae. The M. tuberculosis genes are represented by a letter (A-AC), along with an Rv number or a gene name as annotated in the SangerCentre M. tuberculosis database [4]. Genes D, E, F, G, P and R (asterisked) are absent from both M. leprae and C. diphtheriae. In C. diphtheriae, homologs of genes S-AC and A-M were found on two different contigs (represented here as I and II). M. leprae fadE35 (Q; dotted arrow) is a pseudogene.