IADR Abstract Archives
The role of TreR in membrane physiology of Streptococcus mutans
Objectives: The Gram-positive odontopathogen Streptococcus mutans encodes a prolific system of sugar import and metabolic pathways to effectively digest the sugars that comprise the human diet. One of these sugar-specific systems is the trehalose utilization (tre) operon. In the presence of trehalose, the previously characterized regulator of this operon, TreR, specifically activates the transcription of treA, a hydrolase, and treB, a trehalose- specific PTS transporter. The goal of the current work aims to characterize the role of the regulator, TreR, beyond activation of the trehalose utilization operon.
Methods: Using bioinformatic predictions and existing genomic data, it was hypothesized that TreR may also function to regulate the membrane composition of S. mutans, much like the known regulator of fatty acid biosynthesis, FabT. To further characterize the role of treR in membrane homeostasis, physiological profiling assays, transcriptional analysis and discovery of global regulatory mechanisms were utilized to elucidate membrane-specific alternative functions of TreR.
Results: Data obtained from the study suggests that TreR can regulate genes within the fatty acid biosynthesis operon, specifically fabM. This non-canonical function of TreR can alter membrane composition at low pH, as well as reduce membrane permeability. Furthermore, TreR serves a role in survival in the presence of acid and oxidative stressors, as demonstrated using stress-survival assays.
Conclusions: The results of this study demonstrate that loss of TreR results in increased susceptibility of S. mutans to acid and oxidative stress, therefore reducing the competitive ability of the organism. The importance of TreR is articulated by the regulatory role for the protein, beyond local activation of the tre operon, as it contributes to the virulence and overall fitness of Streptococcus mutans through mechanisms yet to be fully defined.
Methods: Using bioinformatic predictions and existing genomic data, it was hypothesized that TreR may also function to regulate the membrane composition of S. mutans, much like the known regulator of fatty acid biosynthesis, FabT. To further characterize the role of treR in membrane homeostasis, physiological profiling assays, transcriptional analysis and discovery of global regulatory mechanisms were utilized to elucidate membrane-specific alternative functions of TreR.
Results: Data obtained from the study suggests that TreR can regulate genes within the fatty acid biosynthesis operon, specifically fabM. This non-canonical function of TreR can alter membrane composition at low pH, as well as reduce membrane permeability. Furthermore, TreR serves a role in survival in the presence of acid and oxidative stressors, as demonstrated using stress-survival assays.
Conclusions: The results of this study demonstrate that loss of TreR results in increased susceptibility of S. mutans to acid and oxidative stress, therefore reducing the competitive ability of the organism. The importance of TreR is articulated by the regulatory role for the protein, beyond local activation of the tre operon, as it contributes to the virulence and overall fitness of Streptococcus mutans through mechanisms yet to be fully defined.