Friday, December 27, 2024
12/27/2024
The ability to withstand sudden spikes in acidity gives Streptococcus mutans, the principle causative agent of dental caries, a growth advantage over acid-sensitive oral bacteria. In most bacteria, non-coding small RNAs (sRNAs) regulate biochemical pathways that respond to environmental stress such as sudden exposure to acidity. However, the potential roles sRNAs play in mitigating acid stress in S. mutans are unknown. Our long-term goal is to define the functions of non-coding RNAs in S. mutans and to apply this knowledge to develop novel ap- proaches to prevent and treat dental caries. Towards attaining this goal, the objective of this application is to define sRNAs that promote acid stress resistance in S. mutans. We recently identified 15 novel sRNAs in S. mu- tans and discovered that the expression of several were significantly altered when the bacterium was exposed to acidity. Based on this data, the central hypothesis of this project is that sRNAs are key regulators of S. mutans’s acid stress response. The rationale for the proposed research is that sRNA-based gene expression control repre- sent a largely untapped reservoir of therapeutic targets that could be exploited to control dental caries. To test our central hypothesis, in the first aim, we will define the functions of two putative acid-responding sRNAs by combining genetic approaches with in vivo RNA-crosslinking and biochemical analyses. In the second aim, using a highly effective sRNA discovery protocol, we will conduct a comprehensive search for acid-responsive sRNAs in S. mutans by exposing the bacterium to a range of acidic conditions. With the successful completion of this project, the expected outcomes include a catalog of novel acid-responding sRNAs in S. mutans and new mecha- nistic models of sRNA function in mitigating acid stress. This work is expected to have a significant impact be- cause it will reveal new insights into the molecular mechanisms that underpin S. mutans’s ability to overcome acid-induced stress, thereby providing new avenues to control dental caries by disrupting acid-response path- ways.
HHS’ Tracking Accountability in Government Grants System (TAGGS) website provides access to detailed descriptions of grants, loans, aggregated direct payments and other types of financial assistance awarded by the HHS Operating Divisions (OPDIVs) and the Office of the Secretary Staff Divisions (STAFFDIVs).