BIOCHEMICAL STRATAGEM FOR OBLIGATE PARASITISM OF EUKARYOTIC CELLS BY COXIELLA-BURNETII
BIOCHEMICAL STRATAGEM FOR OBLIGATE PARASITISM OF EUKARYOTIC CELLS BY COXIELLA-BURNETII
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DOI：
10.1073/pnas.78.5.3240
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发表时间：
1981-01-01
期刊：
影响因子：
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通讯作者：
WILLIAMS, JC
中科院分区：
文献类型：
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作者：
HACKSTADT, T;WILLIAMS, JC
研究了在近似吞噬体pH条件下，伯纳氏梭菌全细胞对葡萄糖和谷氨酸的体外代谢，以及溶酶性胺对吞噬溶酶体pH的调节对伯纳氏梭菌在鸡胚成纤维细胞中复制的影响。在酸性条件下，葡萄糖和谷氨酸的运输、分解代谢和结合受到高度刺激；在pH 7.0时，这些底物的代谢最低。运输过程是能量依赖的，对氧化磷酸化解偶联剂的抑制高度敏感。使用促溶酶剂氯喹、甲胺或氯化铵提高感染鸡胚成纤维细胞的吞噬溶酶体pH值可抑制伯氏梭菌的增殖，从而证明了体内对酸性条件的吞噬溶酶体的需求。这种明显依赖于吞噬体-溶酶体融合来产生有利于伯氏梭菌复制的pH条件，这表明寄生虫激活的独特生化机制。提出了一种基于H+依赖性刺激细胞功能调节微生物代谢的致病机制。
The in vitro metabolism of glucose and glutamate by whole cells of C. burnetii under conditions designed to approximate the pH within the phagolyosome and the effect of manipulation of the phagolysosomal pH by lysosomotropic amines on the replication of C. burnetii in chicken embryo fibroblasts were examined. The transport, catabolism and incorporation of both glucose and glutamate were highly stimulated by acidic conditions; at pH 7.0 metabolism of these substrates was minimal. The transport processes were energy dependent and highly sensitive to inhibition by uncouplers of oxidative phosphorylation. Increasing the phagolysosomal pH of infected chicken embryo fibroblasts by use of the lysosomotropic agents chloroquine, methylamine or ammonium chloride inhibited the multiplication of C. burnetii, thus demonstrating the in vivo requirement for the acidic conditions of the phagolysosome. This apparent dependence upon phagosome-lysosome fusion to generate pH conditions favorable to C. burnetii replication suggests a unique biochemical mechanism of parasite activation. A pathogenic mechanism based on regulation of microbial metabolism by H+-dependent stimulation of cell function is proposed.