Very long O-antigen chains enhance fitness during Salmonella-induced colitis by increasing bile resistance.
Very long O-antigen chains enhance fitness during Salmonella-induced colitis by increasing bile resistance.
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DOI：
10.1371/journal.ppat.1002918
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发表时间：
2012-09
期刊：
影响因子：
6.7
通讯作者：
Bäumler AJ
中科院分区：
文献类型：
--
作者：
Crawford RW;Keestra AM;Winter SE;Xavier MN;Tsolis RM;Tolstikov V;Bäumler AJ
肠道炎症通过尚未完全解决的机制改变了微生物的腔内栖息地。我们注意到，在小鼠结肠炎模型中，肠道病原体肠炎沙门氏菌血清型鼠伤寒沙门氏菌（S. Typhimurium）中，超长o抗原链组装的FepE调节因子赋予了腔内适应性优势。然而，fepE突变体在组织存活、对补体的抗性或对多粘菌素b的抗性方面没有缺陷。我们进行了代谢物分析，以确定伴随鼠伤寒沙门氏菌诱导的结肠炎的腔内栖息地的变化。该分析表明，鼠伤寒沙门氏菌引起的结肠炎增加了总胆汁酸的腔内浓度。fepE突变显著降低鼠伤寒沙门氏菌对胆汁酸的最小抑制浓度（MIC）。在小鼠结肠炎模型中，口服胆汁酸螯合胆胺树脂可降低鼠伤寒沙门氏菌感染期间结肠内容物中总胆汁酸的浓度，并显著降低fepE基因赋予的腔内适应性优势。总的来说，这些数据表明，非常长的o抗原链在鼠伤寒沙门氏菌的胆汁酸抗性中起作用，这一特性赋予了炎症肠道生长过程中的适应性优势。使用高通量测序方法对肠道微生物群落进行了表征，但对改变其腔内栖息地的因素知之甚少。利用代谢物分析，我们发现在沙门氏菌诱导的结肠炎期间，总胆汁酸的腔内浓度显著升高。在结肠炎期间胆汁浓度升高的情况下，肠沙门氏菌血清型鼠伤寒沙门氏菌（S. Typhimurium）需要非常长的o抗原链来促进肠道生长。相比之下，在胆汁酸浓度正常的情况下，很长的o抗原链对于腔内生长或小鼠器官的生长是必不可少的。因此，沙门氏菌诱导的结肠炎期间胆汁浓度升高改变了腔内栖息地，微生物在这种环境中的生长需要增加胆汁耐药性，在鼠伤寒沙门氏菌的情况下，这是由非常长的o抗原链赋予的。
Intestinal inflammation changes the luminal habitat for microbes through mechanisms that have not been fully resolved. We noticed that the FepE regulator of very long O-antigen chain assembly in the enteric pathogen Salmonella enterica serotype Typhimurium (S. Typhimurium) conferred a luminal fitness advantage in the mouse colitis model. However, a fepE mutant was not defective for survival in tissue, resistance to complement or resistance to polymyxin B. We performed metabolite profiling to identify changes in the luminal habitat that accompany S. Typhimurium-induced colitis. This analysis suggested that S. Typhimurium-induced colitis increased the luminal concentrations of total bile acids. A mutation in fepE significantly reduced the minimal inhibitory concentration (MIC) of S. Typhimurium for bile acids in vitro. Oral administration of the bile acid sequestrant cholestyramine resin lowered the concentrations of total bile acids in colon contents during S. Typhimurium infection and significantly reduced the luminal fitness advantage conferred by the fepE gene in the mouse colitis model. Collectively, these data suggested that very long O-antigen chains function in bile acid resistance of S. Typhimurium, a property conferring a fitness advantage during luminal growth in the inflamed intestine. Microbial communities inhabiting the intestinal tract have been characterized using high-throughput sequencing approaches, but little is known about factors that change their luminal habitat. Using metabolite profiling we discovered that luminal concentrations of total bile acids become significantly elevated during Salmonella-induced colitis. Very long O-antigen chains of Salmonella enterica serotype Typhimurium (S. Typhimurium) were required for luminal growth in the presence of such elevated bile concentrations during colitis. In contrast, very long O-antigen chains were dispensable for luminal growth in the presence of normal concentrations of bile acids or for growth in organs of mice. Thus, elevated bile concentrations during Salmonella-induced colitis change the luminal habitat and microbial growth in this environment requires increased bile resistance, which in case of S. Typhimurium is conferred by very long O-antigen chains.
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影响因子：
3.6
作者：
Gunn, JS;Lim, KB;Miller, SI
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