Dataset Information

Revelation of AbfR in Regulation of Mismatch Repair and Energy Metabolism in S. epidermidis by Integrated Proteomic and Metabolomic Analysis

ABSTRACT: Staphylococcus epidermidis is a common causative of nosocomial infections associated with indwelling medical devices. To date, the mechanisms of the pathogenicity and drug resistance of S. epidermidis have not been clearly elucidated. AbfR has been previously identified as an oxidation-sensing regulator that regulates bacterial aggregation and biofilm formation by responding to oxidative stress in S. epidermidis; however, the regulatory pathways of AbfR are underexplored. In this study, we investigated the oxidation-sensing regulatory mechanism of AbfR using TMT10-plex labelling quantitative proteomic and untargeted metabolomic approaches. Integrated analysis of two omics datasets indicated that abfR depletion influenced nucleic acid metabolism and activated the DNA mismatch repair pathway. In addition, several energy-related metabolic pathways, including tricarboxylic acid (TCA) cycle, glycolysis, and arginine metabolism, were remarkably impacted by the deletion of abfR. This study revealed the regulatory networks of the transcription factor AbfR from a multi-omics view and demonstrated that AbfR played a broad role in not only mismatch repair but also energy metabolism, enabling S. epidermidis to constantly sense and adapt to environmental stress.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Staphylococcus Epidermidis Rp62a Bacteria

DISEASE(S): Disease Free

SUBMITTER: Lei Gu

LAB HEAD: Hu Zhou

PROVIDER: PXD020096 | Pride | 2020-07-29

REPOSITORIES: Pride

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Publications

Revelation of AbfR in regulation of mismatch repair and energy metabolism in S. epidermidis by integrated proteomic and metabolomic analysis.

Gu Lei L Liu Xing X Wang Yu-Qiu YQ Zhou Yan-Ting YT Zhu Hong-Wen HW Huang Jin J Lan Le-Fu LF Zheng Jing J Yang Cai-Guang CG Zhou Hu H

Journal of proteomics 20200722

Staphylococcus epidermidis is a common causative of nosocomial infections associated with indwelling medical devices. To date, the mechanisms of the pathogenicity and drug resistance of S. epidermidis have not been clearly elucidated. AbfR has been previously identified as an oxidation-sensing regulator that regulates bacterial aggregation and biofilm formation by responding to oxidative stress in S. epidermidis; however, the regulatory pathways of AbfR are underexplored. In this study, we inves ...[more]

PMID: 32711166

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Project description:Biofilm formation is considered the most important factor involved in pathogenicity of Staphylococcus epidermidis.We investigated the role of two-component signal transduction system (TCS) srrAB, which was up-regulated under micro-aerobic condition, in the growth and biofilm formation of S. epidermidis.AsrrA-deficient mutant (M-bM-^HM-^FsrrA) derived from S. epidermidis1457 (SE1457), exhibited dramatic reduction in growth and biofilm formation underboth aerobic and micro-aerobic conditions, and more sensitive to several different types of antimicrobial agents, H2O2 and SDS. In New Zealand Rabbit model of S. epidermidis biofilm infection, M-bM-^HM-^FsrrA hardly formed biofilm compared to that of SE1457. Phenotypic alteration was restored to the wide-type levelwhen srrAB were complemented into M-bM-^HM-^FsrrA. Further study found that the initial adherence capacity and production of polysaccharide intercellular adhesion (PIA) in M-bM-^HM-^FsrrA were decreased, while extracellular DNA (eDNA) was increased. Transcriptional Analysisby qRT-PCR demonstrated that expression level of icaRin M-bM-^HM-^FsrrA was up-regulated compared to that of SE1457 under aerobic condition, while down-regulated under micro-aerobic condition;icaA and altE were down-regulated under both conditions. Expression of genes involved in respiratory metabolism, such as qoxB(quinol oxidase polypeptide II), ctaA(heme A synthase), and pfl(pyruvate formatelyase), etc. were down-regulated in M-bM-^HM-^FsrrAunder both conditions. Electrophoretic mobility shift assay (EMSA) revealed that phosphorylated SrrA bound to the promoter regions of icaR, icaA, atlE, qoxB,ctaA, andpflB just like binding its own promoter region srr. Taken together, our results demonstrate that srrAB may provide a mechanistic link between respiratory metabolism, environmental signals, and regulation of biofilm formation in S. epidermidis. Microarrays covering different S. epidermidis genomes were used to assess the impact of the two component system srrAB on growth and biofilm formation, by comparing WT with srrA mutant transcriptomes

Project description:Background: Lysine succinylation is a newly identified PTM, which exists widely from prokaryotes to eukaryotes and participates in various cellular processes, especially in the metabolic processes. Staphylococcus epidermidis is a commensal bacterium in the skin, which attracts more attention as a pathogen, especially in immunocompromised patients and neonates by attaching to medical devices and forming biofilms. However, the significance of lysine succinylation in proteins of Staphylococcus epidermidis has not been investigated. Materials and methods: Using antibody affinity enrichment followed by LC-MS/MS analysis, we examined the succinylome of Staphylococcus epidermidis (ATCC®12228™). Then, bioinformatics analysis was performed, including Gene Ontology, KEGG enrichment, motif characterization, secondary structure, protein-protein interaction, and BLAST analysis. Results: A total of 1557 succinylated lysine sites in 649 proteins were identified in Staphylococcus epidermidis (ATCC 12228). Among these succinylation proteins, GO annotation showed that proteins related to metabolic processes and binding activity accounted for the most based on the analysis of biological process and molecular function, respectively. KEGG pathway characterization indicated that proteins associated with the glycolysis/ gluconeogenesis, and citrate cycle (TCA cycle) pathway were more likely to be succinylated. Moreover, 13 conserved motifs were identified. The specific motif KsuD was conserved in model prokaryotes and eukaryotes. Succinylated proteins with this motif were highly enriched in the glycolysis/gluconeogenesis pathway. One succinylation site(K144) was identified in S-ribosylhomocysteine lyase, a key enzyme in the quorum sensing system, indicating the regulatory role succinylation may play in bacterial processes. Furthermore, 15 succinyltransferases and 18 desuccinylases(erasers) were predicted in S.epidermidis by BLAST analysis. Conclusions: We performed the first comprehensive profile of succinylation in Staphylococcus epidermidis and illustrated the significant role succinylation may play in energy metabolism, QS system, and other bacterial behaviors. This study may be a fundamental basis to investigate the underlying mechanisms of colonization, virulence, and infection of S. epidermidis, as well as provide a new insight into regulatory effects succinylation may lay on metabolic processes.

Dataset Information

Revelation of AbfR in Regulation of Mismatch Repair and Energy Metabolism in S. epidermidis by Integrated Proteomic and Metabolomic Analysis

Publications

Revelation of AbfR in regulation of mismatch repair and energy metabolism in S. epidermidis by integrated proteomic and metabolomic analysis.

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