Streptococcus mitisis a normal member of the human oral microbiota and a leading opportunistic pathogen causing infective endocarditis (IE). Despite the complex interactions betweenS. mitisand human host, understanding ofS. mitisphysiology, as well as its mechanisms of adaptation to host-associated environments, is inadequate, especially when compared with other IE bacterial pathogens. This study reports growth-promoting effects of human serum onS. mitisand other pathogenic streptococci,

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... ngS. oralis,S. pneumoniae, andS. agalactiae. Using transcriptomic analyses we identified that, with the addition of human serum,S. mitisdown-regulates uptake systems for metal ions and sugars, fatty acid biosynthetic genes, and genes involved in stress response and other processes related with growth and replication.S. mitisup-regulates uptake systems for amino acids and short peptides in response to human serum. Zinc availability and environmental signals sensed by the induced short peptide binding proteins were not sufficient to confer the seen growth-promoting effects. More investigation is required to establish the mechanism for growth promotion. Overall, our study contributes to the fundamental understanding ofS. mitisphysiology under host-associated conditions.