Human serum supplementation promotes Streptococcus mitis growth and induces specific transcriptomic responses

Streptococcus mitis is a normal member of the human oral microbiota and a leading opportunistic pathogen causing infective endocarditis (IE). Despite the complex interactions between S. mitis and human host, understanding of S. mitis physiology, 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 on S. mitis and other pathogenic streptococci, including S. oralis, S. pneumoniae, and S. agalactiae. Using transcriptomic analyses we identified that, with the addition of human serum, S. mitis down-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. mitis up-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 of S. mitis physiology under host-associated conditions. Significance S. mitis is exposed to human serum components during commensalism in the human mouth and bloodstream pathogenesis. However, the physiological effects of serum components on this bacterium remain unclear. Using transcriptomic analyses, S. mitis biological processes that respond to the presence of human serum were revealed, providing the fundamental understanding of S. mitis adaptations towards human host conditions.