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Bifidobacterium species are known for their ability to inhabit various habitats and are often regarded as the first colonisers of the human gut. In the present work, we have used comparative genomics to identify conserved genomic signatures specific to Bifidobacterium species associated with the human gut. Our approach discovered five genomic signatures with varying lengths and confidence. Among the predicted five signatures, a 1790 bp multi-drug resistance (MDR) signature was found to be remarkably specific to only those species that can colonise the human gut. The signature codes for a membrane transport protein belonging to the major facilitator superfamily (MFS) generally involved in MDR. Phylogenetic analyses of the MDR signature suggest a lineage-specific evolution of the MDR signature in bifidobacteria colonising the human gut. Functional annotation led to the discovery of two conserved domains in the protein; a catalytic MFS domain involved in the efflux of drugs and toxins, and a regulatory cystathionine-β-synthase (CBS) domain that can interact with adenosyl-carriers. Molecular docking simulation performed with the modelled tertiary structure of the MDR signature revealed the putative functional role of the covalently linked domains. The MFS domain displayed a high affinity towards various protein synthesis inhibitor antibiotics and human bile acids, whereas the C-terminally linked CBS domain exhibited favourable binding with molecular structures of ATP and AMP. Therefore, we believe that the predicted signature represents a niche-specific survival trait involved in bile and antibiotic resistance, imparting an adaptive advantage to the Bifidobacterium species colonising the human gut. [ABSTRACT FROM AUTHOR]

Little is known about the bacteria that reside in the human gallbladder and the mechanisms that allow them to survive within this harsh environment. Here we describe interactions between two strains from a human bile sample, one Ruminococcus gauvreauii (IPLA60001), belonging to the Lachnospiraceae family, and the other, designated as Ruminococcoides bili (IPLA60002 T ; DSM 110008) most closely related to Ruminococcus bromii within the family Ruminococcaceae. We provide evidence for bile salt resistance and sporulation for these new strains. Both differed markedly in their carbohydrate metabolism. The R. bili strain mainly metabolized resistant starches to form formate, lactate and acetate. R. gauvreauii mainly metabolized sugar alcohols, including inositol and also utilized formate to generate acetate employing the Wood Ljungdahl pathway. Amino acid and vitamin biosynthesis genomic profiles also differed markedly between the two isolates, likely contributing to their synergistic interactions, as revealed by transcriptomic analysis of cocultures. Transcriptome analysis also revealed that R. gauvreauii IPLA60001 is able to grow using the end-products of starch metabolism formed by the R. bili strain such as formate, and potentially other compounds (such as ethanolamine and inositol) possibly provided by the autolytic behavior of R. bili. IMPORTANCE Unique insights into metabolic interaction between two isolates; Ruminococcus gauvreauii IPLA60001 and Ruminococcoides bili IPLA60002, from the human gallbladder, are presented here. The R. bili strain metabolized resistant starches while R. gauvreauii failed to do so but grew well on sugar alcohols. Transcriptomic analysis of cocultures of these strains, provides new data on the physiology and ecology of two bacteria from human bile, with a particular focus on cross-feeding mechanisms. Both biliary strains displayed marked resistance to bile and possess many efflux transporters, potentially involved in bile export. However, they differ markedly in their amino acid catabolism and vitamin synthesis capabilities, a feature that is therefore likely to contribute to the strong synergistic interactions between these strains. This is therefore the first study that provides evidence for syntrophic metabolic cooperation between bacterial strains isolated from human bile.

Introduction. Salmonella enterica serovar Typhi ( S . Typhi) is the etiological agent of typhoid fever. To establish an infection in the human host, this pathogen must survive the presence of bile salts in the gut and gallbladder. Hypothesis. S . Typhi uses multiple genetic elements to resist the presence of human bile. Aims. To determine the genetic elements that S . Typhi utilizes to tolerate the human bile salt sodium deoxycholate. Methodology. A collection of S . Typhi mutant strains was evaluated for their ability to growth in the presence of sodium deoxycholate and ox-bile. Additionally, transcriptomic and proteomic responses elicited by sodium deoxycholate on S . Typhi cultures were also analysed. Results. Multiple transcriptional factors and some of their dependent genes involved in central metabolism, as well as in cell envelope, are required for deoxycholate resistance. Conclusion. These findings suggest that metabolic adaptation to bile is focused on enhancing energy production to sustain synthesis of cell envelope components exposed to damage by bile salts.