Oxidative Stress and Pathogenesis of Streptococcus mutans

Streptococcus mutans is able to prosper in the oral cavity and adapt to severe changes in nutrient availability, pH, and oxygen concentration, ultimately causing the disease dental caries. NADH oxidase couples oxygen metabolism and acid production pathways by reducing oxygen and recycling NAD⁺ for sugar fermentation. Along with NADH oxidase, superoxide dismutase is implicated in oxygen stress survival. Objectives: Analyze the role of NADH oxidase in oxygen and acid metabolism, and ascertain how disruption of these pathways affects the ability of the organism to cause disease. Methods: Insertional mutagenesis was used to construct mutations in the NADH oxidase (noxA) and superoxide dismutase (sod) genes individually and in combination. The ability of these strains to survive stress, metabolize both acid and oxygen, and to infect and cause disease in animal models was assessed. Results: The noxA gene encodes the major NADH oxidase, accounting for 40% of the oxygen consumption by the organism. In the absence of NoxA, activity of other oxygen metabolizing enzymes, such as Sod, were increased. Although NADH recycling was disrupted, the ability to metabolize sugar was not diminished. While, the ability to survive acid stress was unaffected, the ability to grow in acidic conditions was reduced. The sod, noxA, and noxA/sod mutant strains demonstrated decreased ability to infect the oral cavity of rats, and to cause disease in a moth larvae model. Conclusion: Our results suggest that the inability of the noxA mutant strain to consume oxygen has a negative impact on the ability of S. mutans to infect and cause disease. The disruption of the oxygen metabolizing pathways, through noxA and sod, may lead to novel drug targets, and a way to control the growth of the organism and diminish the incidence of dental caries. This work supported by Training Program in Oral Science T32DE007202, NIDCR DE13683.