Key Laboratory of Medical Molecular Virology, Institute of Biomedical Sciences and Medical Microbiology, Fudan University, Shanghai, China.
Infect Immun. 2012 Apr;80(4):1381-9. doi: 10.1128/IAI.06370-11. Epub 2012 Jan 30.
Phthiocerol dimycocerosates (PDIMs) and structurally related phenolic glycolipids (PGLs) are complex cell wall lipids unique to pathogenic mycobacteria. While these lipids have been extensively studied in recent years, there are conflicting reports on some aspects of their biosynthesis and on the role of PDIMs and especially PGLs in virulence of Mycobacterium tuberculosis. This has been complicated by the natural deficiency of PGLs in many clinical strains of M. tuberculosis and the frequent loss of PDIMs in laboratory M. tuberculosis strains. In this study, we isolated seven mutants of Mycobacterium marinum deficient in PDIMs and/or PGLs in which multiple genes of the PDIM/PGL biosynthetic locus were disrupted by transposon insertion. Zebrafish infection experiments showed that M. marinum strains lacking one or both of these lipids were avirulent, suggesting that both PDIMs and PGLs are required for virulence. We also found that these strains were hypersensitive to antibiotics and exhibited increased cell wall permeability. Our studies provide new insights into the biosynthesis of PDIMs/PGLs and may help us to understand the role of PDIMs and PGLs in M. tuberculosis virulence.
Phthiocerol dimycocerosates (PDIMs) 和结构相关的酚基甘油二脂 (PGLs) 是分枝杆菌属中特有的复杂细胞壁脂质。虽然近年来这些脂质已被广泛研究，但它们的生物合成的一些方面以及 PDIMs 特别是 PGLs 在结核分枝杆菌毒力中的作用存在相互矛盾的报道。这使得 M. tuberculosis 的许多临床株天然缺乏 PGLs，而实验室 M. tuberculosis 株中 PDIMs 经常丢失变得复杂。在这项研究中，我们分离了七种缺乏 PDIMs 和/或 PGLs 的 Mycobacterium marinum 突变株，这些突变株通过转座子插入破坏了 PDIM/PGL 生物合成基因座的多个基因。斑马鱼感染实验表明，缺乏这两种脂质中的一种或两种的 M. marinum 株均无致病性，表明 PDIMs 和 PGLs 均是毒力所必需的。我们还发现这些菌株对抗生素敏感，细胞壁通透性增加。我们的研究为 PDIMs/PGLs 的生物合成提供了新的见解，并可能有助于我们了解 PDIMs 和 PGLs 在结核分枝杆菌毒力中的作用。
