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首页> 外文期刊>Infection and immunity >Lipids of Putative Relevance to Virulence in Mycobacterium tuberculosis: Correlation of Virulence with Elaboration of Sulfatides and Strongly Acidic Lipids
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Lipids of Putative Relevance to Virulence in Mycobacterium tuberculosis: Correlation of Virulence with Elaboration of Sulfatides and Strongly Acidic Lipids

机译：与结核分枝杆菌毒性有关的脂质：毒性与硫化物和强酸性脂质的关系

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From examination of some 40 patient strains of Mycobacterium tuberculosis, a statistically very significant correlation (Spearman's rho) can be drawn between the root index of virulence for the guinea pig (D. A. Mitchison) and the ability of the individual strains to elaborate strongly acidic lipids (SAL) in culture. These include both sulfatides (SL) and phospholipids (PL). Since essentially all, if indeed not all, of the virulent and only few attenuated strains are prolific in elaborating SAL, this criterion may be a necessary requirement for the expression of virulence in M. tuberculosis. Tested by chi-square, this premise is seen to be statistically and pragmatically highly significant. We speculate that SL may contribute to the pathogenesis of tuberculosis because of a demonstrable activity directed against host liver mitochondrial membranes (manuscript in preparation) and its synergistic potentiation of the specific toxicity of trehalose dimycolate (cord factor). The activity may also be expressed against phagosomal and lysosomal membranes within macrophages. Because of their strongly anionic character, SL and PL may interact with cationic sites on lysosomal hydrolases with resultant immobilization and/or inactivation of the enzymes. By a similar mechanism, these ionic lipids may alter the activity of bactericidal basic proteins, previously recognized in the lysosomal armamentarium. Since a minor but significant fraction of demonstrably attenuated strains is nevertheless prolific in SL or SAL elaboration, this facility alone is evidently not a sufficient criterion for expression of virulence.
机译：通过检查约40例结核分枝杆菌的患者菌株，可以得出豚鼠毒力的根指数（DA Mitchison）与个体能力之间的统计学上非常显着的相关性（斯皮尔曼氏Rho）。菌株以在培养中制备强酸性脂质（SAL）。这些包括硫化物（SL）和磷脂（PL）。由于基本上所有（即使不是全部）强毒力和减毒菌株也很少，因此在制定SAL时该标准可能是表达毒力的必要条件。结核病。经卡方检验，该前提在统计学和语用上都具有高度意义。我们推测SL可能是由于针对宿主肝线粒体膜（制备中的手稿）具有明显的活性及其对海藻糖二甲藻酸酯（绳因子）的特异性毒性的协同增效作用而导致的。还可以针对巨噬细胞内的吞噬和溶酶体膜表达活性。由于它们的强阴离子特性，SL和PL可能与溶酶体水解酶上的阳离子位点相互作用，从而导致酶的固定化和/或失活。通过类似的机制，这些离子脂质可能会改变溶酶体武器库中先前公认的杀菌碱性蛋白的活性。由于在SL或SAL加工过程中，尽管有少量但可证明的减毒株，仍然是多产的，因此单独使用这种设施显然不足以表达毒力。

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