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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Lipooligosaccharide is required for the generation of infectious elementary bodies in Chlamydia trachomatis
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Lipooligosaccharide is required for the generation of infectious elementary bodies in Chlamydia trachomatis

机译：沙眼衣原体中感染性基本体的生成需要脂联低聚糖

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摘要

Lipopolysaccharides (LPS) and lipooligosaccharides (LOS) are the main lipid components of bacterial outer membranes and are essential for cell viability in most Gram-negative bacteria. Here we show that small molecule inhibitors of LpxC [UDP-3-O-(R-3-hydrox-ymyristoyl)-GlcNAc deacetylase], the enzyme that catalyzes the first committed step in the biosynthesis of lipid A, block the synthesis of LOS in the obligate intracellular bacterial pathogen Chlamydia trachomatis. In the absence of LOS, Chlamydia remains viable and establishes a pathogenic vacuole ("inclusion") that supports robust bacterial replication. However, bacteria grown under these conditions were no longer infectious. In the presence of LpxC inhibitors, replicative reticulate bodies accumulated in enlarged inclusions but failed to express selected late-stage proteins and transition to elementary bodies, a Chlamydia developmental form that is required for invasion of mammalian cells. These findings suggest the presence of an outer membrane quality control system that regulates Chlamydia developmental transition to infectious elementary bodies and highlights the potential application of LpxC inhibitors as unique class of antichlamydial agents.
机译：脂多糖（LPS）和脂寡糖（LOS）是细菌外膜的主要脂质成分，对于大多数革兰氏阴性细菌的细胞生存力至关重要。在这里，我们显示了LpxC的小分子抑制剂[UDP-3-O-（R-3-羟基-肉豆蔻酰基）-GlcNAc脱乙酰基酶]，该酶催化脂质A的生物合成中第一个重要步骤，阻断LOS的合成在专一的细胞内细菌病原体沙眼衣原体中。在没有LOS的情况下，衣原体仍保持活力并建立了支持强大细菌复制的致病性液泡（“包含物”）。但是，在这些条件下生长的细菌不再具有传染性。在存在LpxC抑制剂的情况下，复制性网状体堆积在扩大的内含物中，但未能表达选定的后期蛋白质并过渡到基本体，即衣原体的发育形式，是入侵哺乳动物细胞所必需的。这些发现表明存在外膜质量控制系统，该系统调节衣原体向传染性基本体的发育过渡，并突出了LpxC抑制剂作为独特的抗衣原体药物类的潜在应用。

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  • 作者

    Bidong D. Nguyen; Doreen Cunningham; Xiaofei Liang; Xin Chen; Eric J. Toone; Christian R. H. Raetz; Pei Zhou; Raphael H. Valdivia;

  • 作者单位

    Department of Molecular Genetics and Microbiology and Center for Microbial Pathogenesis, Duke University Medical Center, Durham, NC 27710;

    Department of Biological and Physical Sciences, Saint Augustine's College, Raleigh, NC 27610;

    Department of Chemistry, Duke University, Durham, NC 27708;

    Department of Chemistry, Duke University, Durham, NC 27708,School of Pharmaceutical and Life Sciences, Changzhou University, Changzhou 213164, People's Republic of China;

    Department of Chemistry, Duke University, Durham, NC 27708;

    Department of Biochemistry, Duke University Medical Center, Durham, NC 27710;

    Department of Biochemistry, Duke University Medical Center, Durham, NC 27710;

    Department of Molecular Genetics and Microbiology and Center for Microbial Pathogenesis, Duke University Medical Center, Durham, NC 27710;

  • 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

    anti-infectives;

    机译：抗感染;

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