Involvement of NADH Oxidase in Competition and Endocarditis Virulence in Streptococcus sanguinis.

Xiuchun Ge,Fanxiang Kong,Lei Chen,Fadi Elrami,Weihua Chen,Ping Xu,Yang Yu,Min Zhang,Todd Kitten,A Camilli

doi:10.1128/iai.01203-15

Abstract

Here, we report for the first time that the Streptococcus sanguinis nox gene encoding NADH oxidase is involved in both competition with Streptococcus mutans and virulence for infective endocarditis. An S. sanguinis nox mutant was found to fail to inhibit the growth of Streptococcus mutans under microaerobic conditions. In the presence of oxygen, the recombinant Nox protein of S. sanguinis could reduce oxygen to water and oxidize NADH to NAD+. The oxidation of NADH to NAD+ was diminished in the nox mutant. The nox mutant exhibited decreased levels of extracellular H2O2; however, the intracellular level of H2O2 in the mutant was increased. Furthermore, the virulence of the nox mutant was attenuated in a rabbit endocarditis model. The nox mutant also was shown to be more sensitive to blood killing, oxidative and acid stresses, and reduced growth in serum. Thus, NADH oxidase contributes to multiple phenotypes related to competitiveness in the oral cavity and systemic virulence.

Highlights

We report for the first time that the Streptococcus sanguinis nox gene encoding NADH oxidase is involved in both competition with Streptococcus mutans and virulence for infective endocarditis
To examine whether the nox gene is involved in competition, the effect of the nox deletion on the inhibition of S. mutans was assessed on brain heart infusion (BHI) agar plates under microaerobic conditions
The mutation of the nox gene in SK36 produced an effect that was similar to that of catalase addition (Fig. 1). These data suggest that the nox gene is involved in the competition of S. sanguinis with S. mutans, and that the decreased H2O2 secretion is responsible for the diminished inhibition of S. mutans

Summary

Introduction

We report for the first time that the Streptococcus sanguinis nox gene encoding NADH oxidase is involved in both competition with Streptococcus mutans and virulence for infective endocarditis. An S. sanguinis nox mutant was found to fail to inhibit the growth of Streptococcus mutans under microaerobic conditions. There are two genes, nox-1 and nox-2, encoding NADH oxidases in Streptococcus mutans [2, 3]. The efficiency of competence for genetic transformation was significantly altered in a S. pneumoniae nox mutant [4]. These data imply NADH oxidase is important for multiple biological functions in streptococci. We found the nox gene was involved in competition with S. mutans as well as virulence for IE and examined the possible mechanisms by which the nox gene could affect the competition and IE

Methods

Results

Conclusion