ACQUISITION AND SYNTHESIS OF FOLATES BY OBLIGATE INTRACELLULAR BACTERIA OF THE GENUS CHLAMYDIA
ACQUISITION AND SYNTHESIS OF FOLATES BY OBLIGATE INTRACELLULAR BACTERIA OF THE GENUS CHLAMYDIA
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DOI：
10.1172/jci116055
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发表时间：
1992-11-01
影响因子：
15.9
通讯作者：
MCCLARTY, G
中科院分区：
文献类型：
--
作者：
FAN, HZ;BRUNHAM, RC;MCCLARTY, G
我们开展的研究重点是沙眼衣原体 L2、鹦鹉热衣原体 6BC 和鹦鹉热衣原体获取叶酸。使用野生型宿主细胞进行的原位研究结果证实，沙眼衣原体 L2 和鹦鹉热衣原体 6BC 对磺胺类药物敏感，而鹦鹉热衣原体具有耐药性。此外，甲氨蝶呤可以原位抑制沙眼衣原体 L2 和鹦鹉热衣原体，而鹦鹉热衣原体 6BC 则不能。与沙眼衣原体相反，鹦鹉热衣原体菌株均不受甲氧苄啶影响。令人惊讶的是，我们的结果表明所有三种菌株都能够在叶酸耗尽的宿主细胞中有效生长。当在叶酸耗尽的细胞中生长时，鹦鹉热鹦鹉热对磺酰胺变得敏感。通过将外源[H-3]pABA掺入细胞内叶酸并通过检测网状体粗提物中的二氢叶酸合酶活性，证明了所有三种菌株进行从头合成叶酸的能力。还在网状体提取物中检测到二氢叶酸还原酶活性。总的来说，结果表明沙眼衣原体L2、鹦鹉热衣原体和鹦鹉热衣原体6BC都可以从头合成叶酸，然而，菌株直接从宿主细胞转运预先形成的叶酸的能力不同。
We undertook studies focused on folate acquisition by Chlamydia trachomatis L2, Chlamydia psittaci 6BC, and C. psittaci francis. Results from in situ studies, using wild-type host cells, confirmed that C. trachomatis L2 and C. psittaci 6BC are sensitive to sulfonamides whereas C. psittaci francis is resistant. In addition C. trachomatis L2 and C. psittaci francis were inhibited by methotrexate in situ whereas C. psittaci 6BC was not. In contrast to C. trachomatis, neither C. psittaci strain was affected by trimethoprim. Surprisingly our results indicate that all three strains are capable of efficient growth in folate-depleted host cells. When growing in folate-depleted cells C. psittaci francis becomes sensitive to sulfonamide. The ability of all three strains to carry out de novo folate synthesis was demonstrated by following the incorporation of exogenous [H-3]pABA into intracellular folates and by detecting dihydropteroate synthase activity in reticulate body crude extract. Dihydrofolate reductase activity was also detected in reticulate body extract. In aggregate the results indicate that C. trachomatis L2, C. psittaci francis, and C. psittaci 6BC can all synthesize folates de novo, however, strains differ in their ability to transport preformed folates directly from the host cell.