Of mice, men, and elephants:Mycobacterium tuberculosis cell envelope lipids and pathogenesis
Lee W. Riley
Lee W. Riley
Published June 1, 2006
Citation Information: J Clin Invest. 2006;116(6):1475-1478. https://doi.org/10.1172/JCI28734.
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Commentary

Of mice, men, and elephants:Mycobacterium tuberculosis cell envelope lipids and pathogenesis

Abstract

Mycolic acids and structures attached to them constitute a major part of the protective envelope of Mycobacterium tuberculosis, and for this reason, their role in tuberculosis pathogenesis has been extensively studied. In this issue of the JCI, Rao et al. examine the effect of trans-cyclopropanation of oxygenated mycolic acids attached to trehalose dimycolate (TDM) on the murine immune response to infection (see the related article beginning on page 1660). Surprisingly, they found that an M. tuberculosis mutant lacking trans-cyclopropane rings was hypervirulent in mice. The recent recognition of a hypervirulence phenotype in mice associated with laboratory and clinical M. tuberculosis strains with altered cell wall components has provided new insights into how M. tuberculosis may establish persistent infection. However, to date, characterization of these bioactive products in pathogenesis has been largely reductionistic; the relationship of their effects observed in mice to the persistent infection and tuberculosis caused by M. tuberculosis observed in humans remains obscure.

Authors

Lee W. Riley

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Figure 1

Schematic representation ofM. tuberculosis cell envelope.

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Schematic representation ofM. tuberculosis ...
Three forms of mycolic acids are depicted. α-Mycolates are the most abundant form in M. tuberculosis (orange). It has 2 cyclopropane rings (triangles) in cis configuration. Oxygenated mycolates (keto- and methoxy-, shown in red) have one cyclopropane ring each that is in either cis or trans configuration. They are covalently linked to the arabinogalactan layer, which is linked to the peptidoglycan layer. Other lipid complexes in the cell wall include acyl glycolipids (including TDM) and other complex free lipids (e.g., phthiocerol dimycocerosate) as well as sulfolipids. Lipoarabinomannan is shown linked to the plasma membrane via a phosphodiester bond. Rao et al. (1) found that the oxygenated mycolates of a cmaA2M. tuberculosis mutant lack trans-cyclopropanated rings. Such a change could affect the mycolate layer of the cell envelope, which they claim causes a hyperinflammatory response in mice. Figure adapted and modified with permission from the Annual Review of Biochemistry (11) and Cellular Microbiology (29).