Identification of conserved genomic signatures specific to species colonising the human gut.

Unlabelled: 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 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 species colonising the human gut.

Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03492-4.