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Microbiota-liberated host sugars facilitate post-antibiotic expansion of enteric pathogens

机译:释放微生物群的宿主糖可促进肠道后病原体的抗生素扩展

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摘要

The human intestine, colonized by a dense community of resident microbes, is a frequent target of bacterial pathogens. Undisturbed, this intestinal microbiota provides protection from bacterial infections. Conversely, disruption of the microbiota with oral antibiotics often precedes the emergence of several enteric pathogens. How pathogens capitalize upon the failure of microbiota-afforded protection is largely unknown. Here we show that two antibiotic-associated pathogens, Salmonella enterica serovar Typhimurium (S. typhimurium) and Clostridium difficile, use a common strategy of catabolizing microbiota-liberated mucosal carbohydrates during their expansion within the gut. S. typhimurium accesses fucose and sialic acid within the lumen of the gut in a microbiota-dependent manner, and genetic ablation of the respective catabolic pathways reduces its competitiveness in vivo. Similarly, C. difficile expansion is aided by microbiota-induced elevation of sialic acid levels in vivo. Colonization of gnotobiotic mice with a sialidase-deficient mutant of Bacteroides thetaiotaomicron, a model gut symbiont, reduces free sialic acid levels resulting in C. difficile downregulating its sialic acid catabolic pathway and exhibiting impaired expansion. These effects are reversed by exogenous dietary administration of free sialic acid. Furthermore, antibiotic treatment of conventional mice induces a spike in free sialic acid and mutants of both Salmonella and C. difficile that are unable to catabolize sialic acid exhibit impaired expansion. These data show that antibiotic-induced disruption of the resident microbiota and subsequent alteration in mucosal carbohydrate availability are exploited by these two distantly related enteric pathogens in a similar manner. This insight suggests new therapeutic approaches for preventing diseases caused by antibiotic-associated pathogens.
机译:被致密的微生物群落定居的人肠是细菌病原体的常见靶标。该肠道菌群不受干扰,可保护细菌免受感染。相反,用口服抗生素破坏微生物群通常要先于几种肠道病原体的出现。病原体如何利用微生物菌群负担得起的保护措施的失败尚不清楚。在这里,我们显示了两种与抗生素相关的病原体,肠炎沙门氏菌鼠伤寒沙门氏菌(S. typhimurium)和艰难梭状芽胞杆菌,使用了共同的策略来分解微生物释放的粘膜碳水化合物,使其在肠道内膨胀。鼠伤寒沙门氏菌以微生物群依赖性方式进入肠道腔内的岩藻糖和唾液酸,并且相应分解代谢途径的遗传消融降低了其在体内的竞争力。类似地,艰难梭菌的扩增通过微生物群诱导的体内唾液酸水平的升高来辅助。肠道细菌共生体模型细菌拟杆菌拟唾液酸缺乏的唾液酸酶缺陷型突变体的定殖,可降低唾液酸的游离水平,导致艰难梭菌下调其唾液酸分解代谢途径并显示出受损的扩展。通过外源饮食中游离唾液酸的摄入可以逆转这些作用。此外,常规小鼠的抗生素治疗引起游离唾液酸的尖峰,并且不能分解唾液酸的沙门氏菌和艰难梭菌的突变体均显示出受损的扩展。这些数据表明,这两种远缘相关的肠道病原体以相似的方式利用了抗生素诱导的常驻微生物群的破坏以及随后的粘膜糖利用度的改变。该见解提出了预防由抗生素相关病原体引起的疾病的新治疗方法。

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  • 来源
    《Nature》 |2013年第7469期|96-99|共4页
  • 作者单位

    Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California 94305, USA;

    Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California 94305, USA;

    Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California 94305, USA;

    Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California 94305, USA;

    Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California 94305, USA,Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota 55905, USA;

    Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California 94305, USA;

    Glycobiology Research and Training Center, University of California, San Diego, California 92093, USA;

    Glycobiology Research and Training Center, University of California, San Diego, California 92093, USA;

    department of Population Health and Reproduction, University of California, Davis, California 95616, USA;

    Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California 94305, USA;

    Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California 94305, USA;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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  • 正文语种 eng
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