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- Title
Phosphorylation of GntR reduces Streptococcus suis oxidative stress resistance and virulence by inhibiting NADH oxidase transcription.
- Authors
Niu, Kai; Meng, Yu; Liu, Mingxing; Ma, Zhe; Lin, Huixing; Zhou, Hong; Fan, Hongjie
- Abstract
GntR transcription factor of Streptococcus suis serotype 2 (SS2) is a potential substrate protein of STK, but the regulation mechanisms of GntR phosphorylation are still unclear. This study confirmed that STK phosphorylated GntR in vivo, and in vitro phosphorylation experiments showed that STK phosphorylated GntR at Ser-41. The phosphomimetic strain (GntR-S41E) had significantly reduced lethality in mice and reduced bacterial load in the blood, lung, liver, spleen, and brain of infected mice compared to wild-type (WT) SS2. Electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) experiments demonstrated that the promoter of nox was bound by GntR. The phosphomimetic protein GntR-S41E cannot bind to the promoter of nox, and the nox transcription levels were significantly reduced in the GntR-S41E mutant compared to WT SS2. The virulence in mice and the ability to resist oxidative stress of the GntR-S41E strain were restored by complementing transcript levels of nox. NOX is an NADH oxidase that catalyzes the oxidation of NADH to NAD+ with the reduction of oxygen to water. We found that NADH is likely accumulated under oxidative stress in the GntR-S41E strain, and higher NADH levels resulted in increased amplified ROS killing. In total, we report GntR phosphorylation could inhibit the transcription of nox, which impaired the ability of SS2 to resist oxidative stress and virulence. Author summary: Serine/threonine kinase (STK) of SS2 is involved in various important biological processes, and is crucial to bacteria pathogenicity. Our work here shows that STK can inhibit the transcription of the nox gene by phosphorylating the transcription factor GntR, which weakens the anti-oxidant capacity and virulence. SS2 lacking NOX is more likely to produce the accumulation of NADH under oxidative stimulation, which increases amplified ROS killing.
- Subjects
STREPTOCOCCUS suis; PHOSPHORYLATION; TRANSCRIPTION factors; OXYGEN in water; OXIDATIVE stress; TRANSGENIC organisms; OXYGEN reduction
- Publication
PLoS Pathogens, 2023, Vol 18, Issue 3, p1
- ISSN
1553-7366
- Publication type
Article
- DOI
10.1371/journal.ppat.1011227