Quinones are growth factors for the human gut microbiota.
Quinones are growth factors for the human gut microbiota.
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DOI：
10.1186/s40168-017-0380-5
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发表时间：
2017-12-20
期刊：
影响因子：
15.5
通讯作者：
Lewis K
中科院分区：
文献类型：
--
作者：
Fenn K;Strandwitz P;Stewart EJ;Dimise E;Rubin S;Gurubacharya S;Clardy J;Lewis K
人类肠道微生物群与健康和疾病的许多组成部分有关。然而，肠道中大约25%的细菌种类仍未被培养，这限制了我们正确理解和利用人类微生物群的能力。之前，我们发现在扩散室中原位培养环境细菌可以使未培养的物种生长，这表明自然环境中存在传统培养介质中没有的生长因子。生长因子的一个来源被证明是邻近的细菌，通过共培养，我们从海洋环境中分离出以前未培养的生物，并确定了铁载体是细菌生长因子的主要类别。在这里，我们采用类似的共培养技术来培养来自人类肠道微生物组的细菌并鉴定新的生长因子。通过在共培养实验中测试生长缓慢的菌落对生长较快的邻近细菌的依赖性，鉴定出8对分类上不同的细菌，其中“诱导”分离物在可培养的“辅助”细菌周围形成生长梯度。该集包括两个新种Faecalibacterium sp. kle1255和Sutterella sp. KLE1607，属于抗炎Faecalibacterium属。虽然发现了多种辅助菌株，但大肠杆菌也能够促进所有诱导分离株的生长。大肠杆菌敲除文库的筛选表明，诱导Faecalibacterium sp. KLE1255和其他诱导分离株生长需要甲基萘醌生物合成途径。纯化的甲基萘醌诱导了7/8的分离菌株的生长，鉴定了单个细菌的醌特异性谱，基因组分析表明，甲基萘醌的生物合成能力不完全，但诱导菌株中存在厌氧末端还原酶，表明具有厌氧呼吸能力。我们的数据显示，甲基萘醌是人类肠道微生物群中细菌的主要生长因子。这些生物在分类上是多样化的，包括Faecalibacterium、Bacteroides、Bilophila、Gordonibacter和Sutterella。这表明醌类生物合成的丧失在人类微生物群的许多谱系中独立发生。醌类可用于改善现有的细菌生长介质，或通过促进重要共生体（如粪杆菌）的生长来调节人体肠道微生物群。本文的在线版本（10.1186/s40168-017-0380-5）包含补充材料，可供授权用户使用。
The human gut microbiome has been linked to numerous components of health and disease. However, approximately 25% of the bacterial species in the gut remain uncultured, which limits our ability to properly understand, and exploit, the human microbiome. Previously, we found that growing environmental bacteria in situ in a diffusion chamber enables growth of uncultured species, suggesting the existence of growth factors in the natural environment not found in traditional cultivation media. One source of growth factors proved to be neighboring bacteria, and by using co-culture, we isolated previously uncultured organisms from the marine environment and identified siderophores as a major class of bacterial growth factors. Here, we employ similar co-culture techniques to grow bacteria from the human gut microbiome and identify novel growth factors. By testing dependence of slow-growing colonies on faster-growing neighboring bacteria in a co-culture assay, eight taxonomically diverse pairs of bacteria were identified, in which an “induced” isolate formed a gradient of growth around a cultivatable “helper.” This set included two novel species Faecalibacterium sp. KLE1255—belonging to the anti-inflammatory Faecalibacterium genus—and Sutterella sp. KLE1607. While multiple helper strains were identified, Escherichia coli was also capable of promoting growth of all induced isolates. Screening a knockout library of E. coli showed that a menaquinone biosynthesis pathway was required for growth induction of Faecalibacterium sp. KLE1255 and other induced isolates. Purified menaquinones induced growth of 7/8 of the isolated strains, quinone specificity profiles for individual bacteria were identified, and genome analysis suggests an incomplete menaquinone biosynthetic capability yet the presence of anaerobic terminal reductases in the induced strains, indicating an ability to respire anaerobically. Our data show that menaquinones are a major class of growth factors for bacteria from the human gut microbiome. These organisms are taxonomically diverse, including members of the genus Faecalibacterium, Bacteroides, Bilophila, Gordonibacter, and Sutterella. This suggests that loss of quinone biosynthesis happened independently in many lineages of the human microbiota. Quinones can be used to improve existing bacterial growth media or modulate the human gut microbiota by encouraging the growth of important symbionts, such as Faecalibacterium species. The online version of this article (10.1186/s40168-017-0380-5) contains supplementary material, which is available to authorized users.
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影响因子：
--
作者：
D'Onofrio A;Crawford JM;Stewart EJ;Witt K;Gavrish E;Epstein S;Clardy J;Lewis K
通讯作者：
Lewis K
影响因子：
28.3
作者：
Lagier, Jean-Christophe;Khelaifia, Saber;Raoult, Didier
通讯作者：
Raoult, Didier
影响因子：
4.2
作者：
KINDBERG, C;SUTTIE, JW;NAKAO, H
通讯作者：
NAKAO, H
大肠杆菌K-12的构造框架，单基因敲除突变体：Keio Collection。
影响因子：
9.9
作者：
通讯作者：
--
DOI：
10.1073/pnas.0804812105
发表时间：
2008-10-28
影响因子：
11.1
作者：
Sokol, Harry;Pigneur, Benedicte;Langella, Philippe
通讯作者：
Langella, Philippe