Exploring metabolic pathway reconstruction and genome-wide expression profiling in Lactobacillus reuteri to define functional probiotic features.

Exploring metabolic pathway reconstruction and genome-wide expression profiling in Lactobacillus reuteri to define functional probiotic features.
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DOI:
10.1371/journal.pone.0018783
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发表时间:
2011-04-29
期刊:
影响因子:
3.7
通讯作者:
Versalovic J
Versalovic J
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Saulnier DM;Santos F;Roos S;Mistretta TA;Spinler JK;Molenaar D;Teusink B;Versalovic J

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作为人类微生物组计划的一部分,最近对从人类母乳和胃肠道中分离的四种罗伊氏乳杆菌菌株的基因组进行了测序。初步的基因组比较表明,这些菌株属于两个不同的分支,以前显示不同的抗菌剂生产,生物膜形成,和免疫调节。为了解释在宿主和益生菌中存活的可能机制,我们完成了两种代表每组的母乳来源的分离株的详细基因组比较:一种已建立的益生菌菌株(L. reuteri ATCC 55730)和具有有希望的益生菌特征的菌株(L. reuteri ATCC PTA 6475)。L.的转录组使用菌株特异性微阵列监测不同生长期的罗伊氏菌株,并使用代表这些菌株中存在的所有已知代谢反应的泛代谢模型进行比较。这两种菌株都含有参与肠道存活和持久性的候选基因,如粘液结合蛋白和清除活性氧的酶。在菌株55730中鉴定了预测编码胞外多糖合成的大操纵子。这两种菌株都被预测产生健康促进因子,包括抗菌剂和维生素(叶酸,维生素B12)。此外,一个完整的途径硫胺素生物合成的预测菌株55730中首次在这个物种。通过转录组学比较鉴定负责每个菌株免疫调节特性的候选基因。可以使用代谢建模和转录组学来预测人源性益生菌的生物活性代谢物的产生。这些策略可以促进益生菌的选择和优化,以促进健康,预防和改善疾病。
The genomes of four Lactobacillus reuteri strains isolated from human breast milk and the gastrointestinal tract have been recently sequenced as part of the Human Microbiome Project. Preliminary genome comparisons suggested that these strains belong to two different clades, previously shown to differ with respect to antimicrobial production, biofilm formation, and immunomodulation. To explain possible mechanisms of survival in the host and probiosis, we completed a detailed genomic comparison of two breast milk–derived isolates representative of each group: an established probiotic strain (L. reuteri ATCC 55730) and a strain with promising probiotic features (L. reuteri ATCC PTA 6475). Transcriptomes of L. reuteri strains in different growth phases were monitored using strain-specific microarrays, and compared using a pan-metabolic model representing all known metabolic reactions present in these strains. Both strains contained candidate genes involved in the survival and persistence in the gut such as mucus-binding proteins and enzymes scavenging reactive oxygen species. A large operon predicted to encode the synthesis of an exopolysaccharide was identified in strain 55730. Both strains were predicted to produce health-promoting factors, including antimicrobial agents and vitamins (folate, vitamin B12). Additionally, a complete pathway for thiamine biosynthesis was predicted in strain 55730 for the first time in this species. Candidate genes responsible for immunomodulatory properties of each strain were identified by transcriptomic comparisons. The production of bioactive metabolites by human-derived probiotics may be predicted using metabolic modeling and transcriptomics. Such strategies may facilitate selection and optimization of probiotics for health promotion, disease prevention and amelioration.
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