Bile salt hydrolases shape the bile acid landscape and restrict Clostridioides difficile growth in the murine gut.
Bile salt hydrolases shape the bile acid landscape and restrict Clostridioides difficile growth in the murine gut.
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DOI：
10.1038/s41564-023-01337-7
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发表时间：
2023-04
影响因子：
28.3
通讯作者：
Theriot, Casey M.
中科院分区：
文献类型：
--
作者：
Foley, Matthew H.;Walker, Morgan E.;Stewart, Allison K.;O'Flaherty, Sarah;Gentry, Emily C.;Patel, Shakshi;Beaty, Violet V.;Allen, Garrison;Pan, Meichen;Simpson, Joshua B.;Perkins, Caroline;Vanhoy, Molly E.;Dougherty, Michael K.;McGill, Sarah K.;Gulati, Ajay S.;Dorrestein, Pieter C.;Baker, Erin S.;Redinbo, Matthew R.;Barrangou, Rodolphe;Theriot, Casey M.
胆汁酸（BA）介导人类和微生物细胞之间的串扰，并影响包括艰难梭菌感染（CDI）在内的疾病。胆盐水解酶（BSHs）通过解偶联BA来形成BA池，其底物选择性和对C.困难仍然难以捉摸。在这里，我们调查了肠道菌群乳酸杆菌科（Lactobacillaceae）中BSH的多样性，乳酸杆菌科通常用作益生菌，以及人类肠道微生物组的其他成员。我们在结构上确定了一个预测BSH偏好甘氨酸或牛磺酸底物的循环。具有不同特异性的BSH显示出限制C。艰难梭菌孢子在体外的萌发和生长以及在CDI的临床前体内模型中的定殖。此外，BSH重塑了小鼠肠道中微生物结合胆汁酸（MCBA）的库，这些MCBA可以进一步限制C。艰难梭菌的体外毒力。BSH对缀合的BA的识别限定了所得的BA池，包括膨胀的MCBA。这项工作提供了深入了解BSH机制的结构基础，塑造BA景观和促进殖民抵抗C。很难由肠道微生物组编码的胆盐水解酶形成胆汁酸池，包括微生物缀合的胆汁酸，其影响鼠肠道中的艰难梭菌感染。
Bile acids (BAs) mediate the crosstalk between human and microbial cells and influence diseases including Clostridioides difficile infection (CDI). While bile salt hydrolases (BSHs) shape the BA pool by deconjugating conjugated BAs, the basis for their substrate selectivity and impact on C. difficile remain elusive. Here we survey the diversity of BSHs in the gut commensals Lactobacillaceae, which are commonly used as probiotics, and other members of the human gut microbiome. We structurally pinpoint a loop that predicts BSH preferences for either glycine or taurine substrates. BSHs with varying specificities were shown to restrict C. difficile spore germination and growth in vitro and colonization in pre-clinical in vivo models of CDI. Furthermore, BSHs reshape the pool of microbial conjugated bile acids (MCBAs) in the murine gut, and these MCBAs can further restrict C. difficile virulence in vitro. The recognition of conjugated BAs by BSHs defines the resulting BA pool, including the expansive MCBAs. This work provides insights into the structural basis of BSH mechanisms that shape the BA landscape and promote colonization resistance against C. difficile. Bile salt hydrolases encoded by the gut microbiome shape the bile acid pool, including microbial conjugated bile acids, which impact Clostridioides difficile infection in the murine gut.
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影响因子：
4.8
作者：
Fletcher JR;Erwin S;Lanzas C;Theriot CM
通讯作者：
Theriot CM
影响因子：
30.3
作者：
Girinathan BP;DiBenedetto N;Worley JN;Peltier J;Arrieta-Ortiz ML;Immanuel SRC;Lavin R;Delaney ML;Cummins CK;Hoffman M;Luo Y;Gonzalez-Escalona N;Allard M;Onderdonk AB;Gerber GK;Sonenshein AL;Baliga NS;Dupuy B;Bry L
通讯作者：
Bry L
DOI：
10.1093/bioinformatics/bts565
发表时间：
2012-12-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Fu L;Niu B;Zhu Z;Wu S;Li W
通讯作者：
Li W
一类重要的微生物胆汁酸的生物合成途径。
影响因子：
14.8
作者：
Devlin AS;Fischbach MA
通讯作者：
Fischbach MA
影响因子：
14.8
作者：
Chaudhari SN;Harris DA;Aliakbarian H;Luo JN;Henke MT;Subramaniam R;Vernon AH;Tavakkoli A;Sheu EG;Devlin AS
通讯作者：
Devlin AS