02492nas a2200313 4500000000100000008004100001260001600042653001200058653001500070653001400085653001400099653002500113653003100138653001800169653002400187100001400211700001600225700001200241700001200253700001500265700001500280700001400295245018600309856006900495300001300564490000800577520157900585022001402164 2011 d c2011 Jul 0110aAnimals10aArmadillos10aCell Wall10aGalactans10aMycobacterium leprae10aMycobacterium tuberculosis10aMycolic Acids10aSpecies Specificity1 aBhamidi S1 aScherman MS1 aJones V1 aCrick D1 aBelisle JT1 aBrennan PJ1 aMcNeil MR00aDetailed structural and quantitative analysis reveals the spatial organization of the cell walls of in vivo grown Mycobacterium leprae and in vitro grown Mycobacterium tuberculosis. uhttp://www.jbc.org/content/early/2011/05/09/jbc.M110.210534.long a23168-770 v2863 a

The cell wall of mycobacteria consists of an outer membrane, analogous to that of gram-negative bacteria, attached to the peptidoglycan (PG) via a connecting polysaccharide arabinogalactan (AG). Although the primary structure of these components is fairly well deciphered, issues such as the coverage of the PG layer by covalently attached mycolates in the outer membrane and the spatial details of the mycolic acid attachment to the arabinan have remained unknown. It is also not understood how these components work together to lead to the classical acid-fast staining of mycobacteria. Because the majority of Mycobacterium tuberculosis bacteria in established experimental animal infections are acid-fast negative, clearly cell wall changes are occurring. To address both the spatial properties of mycobacterial cell walls and to begin to study the differences between bacteria grown in animals and cultures, the cell walls of Mycobacterium leprae grown in armadillos was characterized and compared with that of M. tuberculosis grown in culture. Most fundamentally, it was determined that the cell wall of M. leprae contained significantly more mycolic acids attached to PG than that of in vitro grown M. tuberculosis (mycolate:PG ratios of 21:10 versus 16:10, respectively). In keeping with this difference, more arabinogalactan (AG) molecules, linking the mycolic acids to PG, were found. Differences in the structures of the AG were also found; the AG of M. leprae is smaller than that of M. tuberculosis, although the same basic structural motifs are retained.

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