The involvement of the pyruvate dehydrogenase E1alpha subunit, in Streptococcus mutans acid tolerance

Streptococcus mutans, an etiological agent of dental caries, is a normal inhabitant of dental plaque. Two main virulence factors of S. mutans are acidogenicity and aciduricity - the ability to produce acid and survive at low pH, respectively. Metabolic processes, including the catabolism of pyruvate, are finely regulated following acid exposure in S. mutans. Proteome analysis of the S. mutans acid response has shown pyruvate dehydrogenase A (PdhA) is upregulated. PdhA is the E1alphasubunit of the four-enzyme pyruvate dehydrogenase complex, responsible for the heterofermentative catalysis of pyruvate into acetyl-CoA. Acetyl-CoA is subsequently catalyzed into ethanol and acetate yielding additional ATP. This investigation examined the relationships between PdhA, aciduricity, and metabolism in S. mutans. An S. mutans pdhA knockout (PDHAKO) revealed an acid sensitive phenotype, displayed by increased doubling times, and decreased competitiveness in a biofermentor. Quantitative real-time PCR showed pdhA expression increased dramatically during acidic growth and under acid adaptation. Additionally, pdhA expression responded to conditions favoring heterofermentative growth; decreased in the presence of excess glucose, and increased during stationary phase compared with mid-log phase growth. This study demonstrated that in S. mutans, pdhA expression responds to conditions conducive to heterofermentation and deletion of pdhA resulted in decreased aciduricity.