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Streptococcus parasanguinis Transcriptomics Data with and without Exogenous Nitrite

ABSTRACT: Oral commensal streptococci play a large role in mediating microbial homeostasis. Our published findings have demonstrated that hydrogen peroxide (H2O2) produced by oral commensal streptococci can react with salivary nitrite (NO2) and generate peroxynitrite (ONOO-), a potent antimicrobial. We have shown that the combinatorial antimicrobial effects of NO2 and H2O2 produced from the commensal Streptococcus parasanguinis, inhibit the colonization and pathogenesis of oral pathogens to promote homeostasis. Remarkably, S. parasanguinis is highly resistant to the NO2 and ONOO-. However, it remains unclear how S. parasanguinis copes in the presence of nitrosative stress. The goal of this study was to identify mechanisms used by S. parasanguinis to resist NO2-mediated nitrosative stress using a transcriptomics approach. Transcriptomic analysis showed that the competence response regulator, comE, is upregulated in the presence of NO2. Loss of comE resulted in a decrease in biofilm development, H2O2 production, increased acid tolerance and sensitivity to ONOO- compared to wild-type S. parasanguinis. Our data show that ComE is critical for key aspects of S. parasanguinis physiology and potentially impacts this commensal's ability to colonize and modulate homeostasis in the oral cavity.

ORGANISM(S): Streptococcus parasanguinis FW213

PROVIDER: GSE284166 | GEO | 2026/02/01

REPOSITORIES: GEO

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Project description:Peroxynitrite is formed in macrophages by the diffusion-limited reaction of superoxide and nitric oxide. This highly reactive species is capable of causing both oxidative and nitrosative stress in Escherichia coli. Previous studies have focused on the reactions of peroxynitrite with specific proteins or the effects of peroxynitrite on the growth and viability of whole cells. This work shows for the first time the transcriptomic response of E. coli to peroxynitrite, highlighting specific areas targeted by the stress. Upregulation of the cysteine biosynthesis pathway and subsequent identification of an increase in S-nitrosothiol levels suggests S-nitrosylation as a consequence of peroxynitrite exposure. Genes involved in the assembly / repair of iron-sulfur clusters also show enhanced transcription identifying another target of this reactive species. Unexpectedly arginine biosynthesis gene transcription levels were also elevated after treatment with peroxynitrite. Analysis of the negative regulator for these genes, ArgR, showed that the post-translational nitration of tyrosine residues within this protein is responsible for its degradation in vitro. Further upregulation is seen in oxidative stress response genes including katG and ahpCF. Probabilistic modelling of this data identified 5 altered transcription factors in response to peroxynitrite exposure including OxyR and ArgR. Hydrogen peroxide can be present as a contaminant in commercially available peroxynitrite preparations. Transcriptomic analysis of cells treated with hydrogen peroxide also showed an upregulation of oxidative stress response genes; however it did not show increased transcription of many other genes which are upregulated by peroxynitrite suggesting that cellular responses to peroxynitrite and hydrogen peroxide are distinct. Biological experiments (i.e. a comparison of control and plus peroxynitrite cells) were carried out three times, and a dye swap performed for each experiment, providing two technical repeats for each of the three biological repeats. Data from the independent experiments were combined. Genes that were differentially expressed ≥ twofold and displayed and P value of < 0.05 (as determined by a t test) were defined as being statistically significantly differentially transcribed. Additional biological experiments (i.e. a comparison of control and plus hydrogen peroxide cells) were carried out three times, and a dye swap performed for each experiment, providing two technical repeats for each of the three biological repeats. Data from the independent experiments were combined. Genes that were differentially expressed ≥ twofold and displayed and P value of < 0.05 (as determined by a t test) were defined as being statistically significantly differentially transcribed.

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Streptococcus parasanguinis Transcriptomics Data with and without Exogenous Nitrite

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