title: Exploring metabolic pathway reconstruction and genome-wide expression profiling in Lactobacillus reuteri to define functional probiotic features.
abstract: 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 B(12)). 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.
authors.affiliation: Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas, United States of America. Delphine.Saulnier@nizo.nl
authors.forename: Delphine M
authors.initials: DM
authors.lastname: Saulnier
authors.forename: Filipe
authors.initials: F
authors.lastname: Santos
authors.forename: Stefan
authors.initials: S
authors.lastname: Roos
authors.forename: Toni-Ann
authors.initials: TA
authors.lastname: Mistretta
authors.forename: Jennifer K
authors.initials: JK
authors.lastname: Spinler
authors.forename: Douwe
authors.initials: D
authors.lastname: Molenaar
authors.forename: Bas
authors.initials: B
authors.lastname: Teusink
authors.forename: James
authors.initials: J
authors.lastname: Versalovic
mesh_terms: D001422:Bacterial Adhesion; D018441:Biofilms; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D016680:Genome, Bacterial; D006801:Humans; D052200:Limosilactobacillus reuteri / Q000235:genetics*; D053858:Metabolic Networks and Pathways / Q000235:genetics; D008895:Milk, Human / Q000382:microbiology; D005810:Multigene Family; D011134:Polysaccharides / Q000737:chemistry; D019936:Probiotics / Q000378:metabolism*; D013045:Species Specificity; D059467:Transcriptome
chemical_list: D011134:Polysaccharides