結核菌の毒性糖脂質(cord factor)の作用機序

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概要

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• The mechanism of the delayed lethal toxicity of cord factor (trehalose-6, 6'-dimycolate) of <I>Mycobacterium tuberculosis</I> for mice was investigated.<BR>Biochemical damages induced by cord factor in vivo were first studied with the homogenate of mouse liver. The activities of succinate-neotetrazolium reductase, reduced coenzyme Qcytochrome <I>c</I> reductase and the phosphorylation associated with the succinate and β-hydroxybutyrate oxidation werd impaired in livers of mice either intoxicated with cord factor or infected with virulent <I>M. tuberculosis</I>.<BR>To analyse further the site of lesion in the cellular respiratory metabolism by cord factor, the structure and function of mitochondria prepared from the cord factor-intoxicated mice were studied. Cord factor disrupted both <I>in vitro</I> and <I>in vitro</I> the mitochondrial membrane into fragments deficient in the respiratory and phosphorylative activity. The site of functional damage was located in the segment between coenzyme Q-cytochrome <I>b</I> complex and cytochrome c (coupling site II) of the mitochondrial electron transport system. Electron microscopically, mitochondria were markedly swollen and disintegrated by cord factor either <I>in vitro</I> or <I>in vitro</I>. The inner membrane spheres were detached from the swollen inner membrane.<BR>The above structural and functional damage in mitochondria was observed with a number of toxic cord factor-analogs, while mycolic acid, acetylated cord factor and the cord factorinactive semisynthetic analog showed no effect on the mitochondrial structure and function.<BR>Trehalose-6, 6'-dicorynomycolate, the cord factor of <I>Corynebacterium diphtheriae</I>, affected the mitochondrial structure and the oxidative phosphorylation as did the mycobacterial cord factor, whereas neither the crystalline exotoxin of <I>C. diphtheriae</I>, lipopolysaccharides derived from a number of gram-negative bacteria nor the endotoxic glycolipids and lipid A induced the mitochondrial swelling <I>in vitro</I>, indicating that the effect of cord factor on mitochondrial membrane structure is specific to this glycolipid-toxin.<BR>From these results, it was assumed that the above metabolic damage in host-cell mitochondria is the biochemical basis of the toxicity of cord factor.

• 一般社団法人 日本結核病学会の論文

著者

• 加藤 允彦

  国立療養所刀根山病院

関連論文

• 結核の経気感染に関する実験的研究 : (P32で標識したMycobacterium phleiを使つての予備実験)その2.空気中の菌のありかたの違いによる動物体内における菌分布の差について
• 結核菌の毒性糖脂質(cord factor)の作用機序

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