Lactic acid bacteria (LAB) are the most important bacteria in food fermentations. Among the genera included in LAB is the Streptococcus genus, containing a number of species that are commensals and opportunistic pathogens. Up to now only one species in the Streptococcus genus, Streptococcus thermophilus, has been traditionally used as a starter in milk and is considered a domesticated organism. However, Streptococcus macedonicus, belonging to the S. bovis/S. equinus complex (SBSEC), can be also found in milk. In this study, S. macedonicus was fully sequenced and a comparative analysis was performed against all other SBSEC members. According to our analysis, S. macedonicus missed several genes encoding enzymes for the degradation of complex plant carbohydrates typically met in the genome of Streptococcus gallolyticus, indicating a reduced ability to survive in the gastrointestinal tract of herbivores. In addition, two pilus operons necessary for the adhesion of S. gallolyticus to the host and the initiation of infection were absent from the S. macedonicus genome. Adaptation of S. macedonicus to the milk environment was supported by the presence of an extra lactose operon. Finally, the plasmid pSMA198 found in S. macedonicus also provided evidence about the habituation of the species to milk. Our findings support adaptation of S. macedonicus to the rich in nutrients milk environment characterized by diminished biosynthetic capabilities and loss of pathogenicity-related genes in parallel to gene gain events through horizontal gene transfer, similarly to S. thermophilus. Comparative analysis between S. macedonicus and S. thermophilus though revealed numerous species-specific differences at the genomic and proteomic level, suggesting that common strategies can be used by truly divergent organisms during their evolutionary history
