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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Small molecule perimeter defense in entomopathogenic bacteria
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Small molecule perimeter defense in entomopathogenic bacteria

机译：昆虫病原菌中的小分子周边防御

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摘要

Two Gram-negative insect pathogens, Xenorhabdus nematophila and Photorhabdus luminescens, produce rhabduscin, an amido-glycosyl- and vinyl-isonitrile-functionalized tyrosine derivative. Heterologous expression of the rhabduscin pathway in Escherichia coli. precursor-directed biosynthesis of rhabduscin analogs, biochemical assays, and visualization using both stimulated Raman scattering and confocal fluorescence microscopy established rhab-duscin's role as a potent nanomolar-level inhibitor of phenoloxi-dase, a key component of the insect's innate immune system, as well as rhabduscin's localization at the bacterial cell surface. Stimulated Raman scattering microscopy visualized rhabduscin at the periphery of wild-type X. nematophila cells and E. coli cells hetero-logously expressing the rhabduscin pathway. Precursor-directed biosynthesis created rhabduscin mimics in X. nematophila pathway mutants that could be accessed at the bacterial cell surface by an extracellular bioorthogonal probe, as judged by confocal fluorescence microscopy. Biochemical assays using both wild-type and mutant X. nematophila cells showed that rhabduscin was necessary and sufficient for potent inhibition (low nM) of phenploxidases, the enzymes responsible for producing melanin (the hard black polymer insects generate to seal off microbial pathogens). These observations suggest a model in which rhabduscin's physical association at the bacterial cell surface provides a highly effective inhibitor concentration directly at the site of phenoloxidase contact. This class of molecules is not limited to insect pathogens, as the human pathogen Vibrio cholerae also encodes rhabduscin's aglycone, and bacterial cell-coated immunosuppressants could be a general strategy to combat host defenses.
机译：两种革兰氏阴性昆虫病原体Xenorhabdus nematophila和Photorhabdus luminescens产生了rhabduscin，这是一种酰胺基糖基和乙烯基异腈官能化的酪氨酸衍生物。 rhabduscin途径在大肠杆菌中的异源表达。鼠李糖球蛋白类似物的前体定向生物合成，生化测定以及使用受激拉曼散射和共聚焦荧光显微镜的可视化证明，鼠李糖球蛋白作为一种有效的纳摩尔级酚氧化酶抑制剂是昆虫先天免疫系统的关键组成部分，并具有一定的作用。以及rhabduscin在细菌细胞表面的定位。刺激的拉曼散射显微镜在异源表达鼠李糖胞苷途径的野生型嗜线虫嗜血杆菌和大肠杆菌细胞的周围观察到了鼠李糖苷。前体定向的生物合成在嗜油杆菌X.nematophila途径突变体中产生了鼠李素类似物，可通过共聚焦荧光显微镜检查通过细胞外生物正交探针在细菌细胞表面进入。使用野生型和突变型嗜线虫嗜血杆菌的生化分析表明，对于强力抑制（低nM）苯氧化酶（产生黑素的酶（坚硬的黑色聚合物昆虫产生来封闭微生物病原体）），鼠李素是必要且足够的。这些观察结果提出了一种模型，其中在细菌细胞表面上的鼠李糖脂的物理缔合直接在酚氧化酶接触的部位提供了高效的抑制剂浓度。这类分子不仅限于昆虫病原体，因为人类病原体霍乱弧菌还编码鼠李糖苷的糖苷配基，细菌细胞包被的免疫抑制剂可能是对抗宿主防御的一般策略。

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  • 作者

    Jason M. Crawford; Cyril Portmann; Xu Zhang; Maarten B. J. Roeffaers; Jon Clardy;

  • 作者单位

    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115 Department of Microbial and Molecular Systems, Katholieke Universiteit Leuven, B-3001 Heverlee, Belgium;

    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115;

    Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138;

    Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138;

    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115 Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    oxidase inhibitors; innate immunity; natural products; virulence factors;

    机译：氧化酶抑制剂;先天免疫;天然产物;毒力因子;

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