AUTHOR=Korir Michelle L. , Flaherty Rebecca A. , Rogers Lisa M. , Gaddy Jennifer A. , Aronoff David M. , Manning Shannon D. 

TITLE=Investigation of the Role That NADH Peroxidase Plays in Oxidative Stress Survival in Group B Streptococcus

JOURNAL=Frontiers in Microbiology

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2018.02786

DOI=10.3389/fmicb.2018.02786

ISSN=1664-302X

ABSTRACT=<p>Macrophages play an important role in defending the host against infections by engulfing pathogens and containing them inside the phagosome, which consists of a harsh microbicidal environment. However, many pathogens have developed mechanisms to survive inside macrophages despite this challenge. Group B <italic>Streptococcus</italic> (GBS), a leading cause of sepsis and meningitis in neonates, is one such pathogen that survives inside macrophages by withstanding phagosomal stress. Although a few key intracellular survival factors have been identified, the mechanisms by which GBS detoxifies the phagosome are poorly defined. Transcriptional analysis during survival inside macrophages revealed strong upregulation of a putative NADH peroxidase (<italic>npx</italic>) at 1 and 24 h post-infection. A deletion mutant of <italic>npx</italic> (Δ<italic>npx</italic>) was more susceptible to killing by a complex <italic>in vitro</italic> model of multiple phagosomal biochemical/oxidant stressors or by hydrogen peroxide alone. Moreover, compared to an isogenic wild type GBS strain, the Δ<italic>npx</italic> strain demonstrated impaired survival inside human macrophages and a reduced capacity to blunt macrophage reactive oxygen species (ROS) production. It is therefore likely that Npx plays a role in survival against ROS production in the macrophage. A more thorough understanding of how GBS evades the immune system through survival inside macrophages will aid in development of new therapeutic measures.</p>