Oral Commensals Altering Streptococcus mutans Gene Expression

The development of tooth decay, or dental caries, is a complex process that ultimately leads to the demineralization of the enamel due to acid production by microbes in biofilms attached to the tooth's surface. The bacterial interactions occurring within these biofilms between acid-producing bacteria, such as the mutans streptococci, and health-associated commensal streptococci, are thought to be critical determinants of health and disease. Recent evidence suggests that commenals antagonize Streptococcus mutans through interference of cell-cell communication or quorum sensing. Our data show that only direct growth of S. mutans with a commensal can completely abolish this signaling, signifying that contact between the two species is critical. We have also identified other novel gene regulation changes that occur within S. mutans when it is faced with competition by commensals. Documenting and characterizing these modifications will lead to better design of new therapeutics to suppress the growth of caries-causing bacteria.

 
CommensalsAlterSmutansModel.png

Current Model

Direct contact with commensal streptococci (blue cells) leading to S. mutans (direct contact white cells with green outline, non-contact green cells) alterations in gene expression. The subset of S. mutans that is in direct contact with commensals produces a signal that changes behavior for the rest of the population, including those non-contacted S. mutans cells.

 

Project Publications

Direct interactions with commensal streptococci modify intercellular communication behaviors of Streptococcus mutans

Justin R. Kaspar, Kyulim Lee, Brook Richard, Alejandro R. Walker & Robert A. Burne

The formation of dental caries is a complex process that ultimately leads to damage of the tooth enamel from acids produced by microbes in attached biofilms. The bacterial interactions occurring within these biofilms between cariogenic bacteria, such as the mutans streptococci, and health-associated commensal streptococci, are thought to be critical determinants of health and disease. To better understand these interactions, a Streptococcus mutans reporter strain that actively monitors cell–cell communication via peptide signaling was cocultured with different commensal streptococci. Signaling by S. mutans, normally highly active in monoculture, was completely inhibited by several species of commensals, but only when the bacteria were in direct contact with S. mutans. We identified a novel gene expression pattern that occurred in S. mutans when cultured directly with these commensals. Finally, mutant derivatives of commensals lacking previously shown antagonistic gene products displayed wild-type levels of signal inhibition in cocultures. Collectively, these results reveal a novel pathway(s) in multiple health-associated commensal streptococci that blocks peptide signaling and induces a common contact-dependent pattern of differential gene expression in S. mutans. Understanding the molecular basis for this inhibition will assist in the rational design of new risk assessments, diagnostics, and treatments for the most pervasive oral infectious diseases.