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首页> 外文期刊>Journal of bacteriology >Competitive Inhibition of Amino Acid Uptake Suppresses Chlamydial Growth: Involvement of the Chlamydial Amino Acid Transporter BrnQ
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Competitive Inhibition of Amino Acid Uptake Suppresses Chlamydial Growth: Involvement of the Chlamydial Amino Acid Transporter BrnQ

机译：竞争性吸收氨基酸抑制抑制衣原体生长：衣原体氨基酸转运蛋白BrnQ的参与。

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摘要

Chlamydiaceae are obligate intracellular bacterial pathogens that strictly depend on host metabolites, such as nucleotides, lipids, and amino acids. Depletion of amino acids in cell culture media results in abnormal chlamydial development in vitro. Surprisingly, enrichment of certain amino acids also retards chlamydial growth. Our experiments revealed that the antichlamydial effects are largely independent of changes in the host cell transcriptome or proteome and in the major signal transduction pathway modulated by amino acids, the mTOR (mammalian target of rapamycin) pathway. Furthermore, the chlamydial growth inhibition induced by leucine, isoleucine, methionine, or phenylalanine was completely reversed by concomitant addition of valine. In contrast, the growth inhibition induced by serine, glycine, or threonine was not reversed by valine addition. Functional characterization of the only predicted chlamydial transporter for branched-chain amino acids, BrnQ, revealed that it can be blocked by leucine, isoleucine, methionine, or phenylalanine but not by serine, glycine, or threonine. This chlamydial transporter is the only known BrnQ homolog possessing specificity for methionine, suggesting a unique strategy for methionine uptake among gram-negative bacteria. The antichlamydial effects of leucine, isoleucine, methionine, and phenylalanine could be explained as competitive inhibition of the BrnQ transporter and subsequent valine starvation.
机译：衣原体科是专一的细胞内细菌病原体，严格依赖于宿主代谢产物，如核苷酸，脂质和氨基酸。细胞培养基中氨基酸的耗尽会导致体外衣原体发育异常。出人意料的是，某些氨基酸的富集也阻碍了衣原体的生长。我们的实验表明抗衣原体的作用在很大程度上不依赖于宿主细胞转录组或蛋白质组的变化，以及氨基酸调节的主要信号转导途径，即mTOR（雷帕霉素的哺乳动物靶标）途径。此外，亮氨酸，异亮氨酸，蛋氨酸或苯丙氨酸诱导的衣原体生长抑制作用可通过同时添加缬氨酸而完全逆转。相反，添加缬氨酸并不能逆转由丝氨酸，甘氨酸或苏氨酸诱导的生长抑制。唯一预测的支链氨基酸衣原体转运蛋白BrnQ的功能表征表明，它可以被亮氨酸，异亮氨酸，蛋氨酸或苯丙氨酸阻断，但不能被丝氨酸，甘氨酸或苏氨酸阻断。这种衣原体转运蛋白是唯一已知的对蛋氨酸具有特异性的BrnQ同源物，这表明革兰氏阴性细菌对蛋氨酸的摄取具有独特的策略。亮氨酸，异亮氨酸，蛋氨酸和苯丙氨酸的抗衣原体作用可以解释为竞争性抑制BrnQ转运蛋白和随后的缬氨酸饥饿。

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