Influence of excess branched-chain amino acid uptake by Streptococcus mutans in human host cells

Abstract

Oral streptococci, including cariogenic bacterium Streptococcus mutans, comprise a large percentage of human supragingival plaque, which contacts both tooth surfaces and gingiva. Eukaryotic cells are able to take up macromolecules and particles, including bacteria, by endocytosis. Increasing evidence indicates endocytosis may be used as an entry process by bacteria. We hypothesized that some endocytosed bacteria might survive and obtain nutrients, such as amino acids, until they are killed. To verify this hypothesis, we focused on bacterial utilization of branched-chain amino acids (BCAAs; isoleucine, leucine and valine) in host cells. A branched-chain aminotransferase, IlvE (EC 2.6.1.42), has been suggested to play an important role in internal synthesis of BCAAs in S. mutans UA159. Therefore, we constructed an ilvE-deficient S. mutans 109c strain and confirmed that it had similar growth behavior as reported previously. 14C radioactive leucine uptake assays showed that ilvE-deficient S. mutans took up more leucine both inside and outside of host cells. We further clarified that a relative decrease of BCAAs in host cells caused enhanced endocytic and autophagic activity. In conclusion, S. mutans is endocytosed by host cells and may survive and obtain nutrients, such as BCAAs, inside the cells, which might affect cellular functions of host cells.

Correlation of Salivary Occult Blood with the Plasma Concentration of Branched-Chain Amino Acids: A Cross-Sectional Study

“…Interestingly, Streptococcus mutans possesses BCAA aminotransferase activity encoded by iLvE [ 23 ]. iLvE plays a role in the biosynthesis and catabolism of BCAA [ 24 , 25 ] and in S. mutans ’s acid tolerance [ 23 ] and survival after immune-cell phagocytosis [ 26 ]. According to the evidence presented above, oral bacteria that synthesize BCAA are not only associated with periodontal pathogenesis, but may also be involved in the elevation of plasma BCAA levels.…”