Anaerobic Respiration of Escherichia coli in the Mouse Intestine

Anaerobic Respiration of Escherichia coli in the Mouse Intestine
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DOI:
10.1128/iai.05395-11
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发表时间:
2011-10-01
影响因子:
3.1
通讯作者:
Conway, Tyrrell
Conway, Tyrrell
中科院分区:
医学2区
文献类型:
--
作者:
Jones, Shari A.;Gibson, Terri;Conway, Tyrrell

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肠道中居住着一个大型微生物群落,主要由厌氧菌组成,其次是兼性厌氧菌,如大肠杆菌,我们已经证明,它需要好氧呼吸才能在小鼠肠道中成功竞争(S.A.Jones等人,感染。伊蒙。75:4891-4899,2007)。如果兼性厌氧菌有效地降低了肠道中的氧气利用率,那么它们的持续生长也必须依赖于厌氧代谢。为了支持这一观点,缺乏硝酸还原酶或富马酸还原酶的突变体具有极端的定植缺陷。在这里,我们使用链霉素处理的小鼠模型进一步探索无氧呼吸在定植中的作用。我们发现呼吸电子流主要是通过萘醌类物质,将电子传递给细胞色素BD氧化酶和厌氧末端还原酶。我们发现,大肠杆菌在肠道中使用硝酸盐和富马酸,但不使用亚硝酸盐、二甲基亚砜或三甲胺N-氧化物。竞争定殖结果表明,细胞色素BD氧化酶比硝酸还原酶或富马酸还原酶更具优势。当盲肠粘液中的硝酸盐浓度达到亚毫摩尔水平时,缺乏硝酸还原酶的菌株就会击败富马酸还原酶突变株,这表明富马酸是肠道中更重要的厌氧电子受体,因为硝酸盐是限制性的。由于在没有大肠杆菌的情况下硝酸盐含量最高,我们得出结论,在链霉素处理的小鼠大肠中,大肠杆菌是唯一能呼吸硝酸盐的细菌。最后,我们证明了缺乏NarXL调节器(Narg系统的激活子)的突变体,而不是缺乏Narp-NarQ调节器的突变体,具有定植缺陷,这与Narg提供的优势一致。正在出现的情况是,基因调控被调整以平衡末端还原酶的表达,大肠杆菌用来最大限度地提高竞争力,并在肠道中实现尽可能高的种群数量。
The intestine is inhabited by a large microbial community consisting primarily of anaerobes and, to a lesser extent, facultative anaerobes, such as Escherichia coli, which we have shown requires aerobic respiration to compete successfully in the mouse intestine (S. A. Jones et al., Infect. Immun. 75: 4891-4899, 2007). If facultative anaerobes efficiently lower oxygen availability in the intestine, then their sustained growth must also depend on anaerobic metabolism. In support of this idea, mutants lacking nitrate reductase or fumarate reductase have extreme colonization defects. Here, we further explore the role of anaerobic respiration in colonization using the streptomycin-treated mouse model. We found that respiratory electron flow is primarily via the naphthoquinones, which pass electrons to cytochrome bd oxidase and the anaerobic terminal reductases. We found that E. coli uses nitrate and fumarate in the intestine, but not nitrite, dimethyl sulfoxide, or trimethylamine N-oxide. Competitive colonizations revealed that cytochrome bd oxidase is more advantageous than nitrate reductase or fumarate reductase. Strains lacking nitrate reductase outcompeted fumarate reductase mutants once the nitrate concentration in cecal mucus reached submillimolar levels, indicating that fumarate is the more important anaerobic electron acceptor in the intestine because nitrate is limiting. Since nitrate is highest in the absence of E. coli, we conclude that E. coli is the only bacterium in the streptomycin-treated mouse large intestine that respires nitrate. Lastly, we demonstrated that a mutant lacking the NarXL regulator (activator of the NarG system), but not a mutant lacking the NarP-NarQ regulator, has a colonization defect, consistent with the advantage provided by NarG. The emerging picture is one in which gene regulation is tuned to balance expression of the terminal reductases that E. coli uses to maximize its competitiveness and achieve the highest possible population in the intestine.