Dataset Information

Malonyl-proteome profiles of Staphylococcus aureus reveal lysine malonylation modification in enzymes involved in energy metabolism.

ABSTRACT:

Background

Protein lysine malonylation, a novel post-translational modification (PTM), has been recently linked with energy metabolism in bacteria. Staphylococcus aureus is the third most important foodborne pathogen worldwide. Nonetheless, substrates and biological roles of malonylation are still poorly understood in this pathogen.

Results

Using anti-malonyl-lysine antibody enrichment and high-resolution LC-MS/MS analysis, 440 lysine-malonylated sites were identified in 281 proteins of S. aureus strain. The frequency of valine in position -?1 and alanine at +?2 and?+?4 positions was high. KEGG pathway analysis showed that six categories were highly enriched, including ribosome, glycolysis/gluconeogenesis, pentose phosphate pathway (PPP), tricarboxylic acid cycle (TCA), valine, leucine, isoleucine degradation, and aminoacyl-tRNA biosynthesis. In total, 31 malonylated sites in S. aureus shared homology with lysine-malonylated sites previously identified in E. coli, indicating malonylated proteins are highly conserved among bacteria. Key rate-limiting enzymes in central carbon metabolic pathways were also found to be malonylated in S. aureus, namely pyruvate kinase (PYK), 6-phosphofructokinase, phosphoglycerate kinase, dihydrolipoyl dehydrogenase, and F1F0-ATP synthase. Notably, malonylation sites were found at or near protein active sites, including KH domain protein, thioredoxin, alanine dehydrogenase (ALD), dihydrolipoyl dehydrogenase (LpdA), pyruvate oxidase CidC, and catabolite control protein A (CcpA), thus suggesting that lysine malonylation may affect the activity of such enzymes.

Conclusions

Data presented herein expand the current knowledge on lysine malonylation in prokaryotes and indicate the potential roles of protein malonylation in bacterial physiology and metabolism.

SUBMITTER: Shi Y

PROVIDER: S-EPMC7802289 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Publications

Malonyl-proteome profiles of Staphylococcus aureus reveal lysine malonylation modification in enzymes involved in energy metabolism.

Shi Yanan Y Zhu Jingjing J Xu Yan Y Tang Xiaozhao X Yang Zushun Z Huang Aixiang A

Proteome science 20210112 1

<h4>Background</h4>Protein lysine malonylation, a novel post-translational modification (PTM), has been recently linked with energy metabolism in bacteria. Staphylococcus aureus is the third most important foodborne pathogen worldwide. Nonetheless, substrates and biological roles of malonylation are still poorly understood in this pathogen.<h4>Results</h4>Using anti-malonyl-lysine antibody enrichment and high-resolution LC-MS/MS analysis, 440 lysine-malonylated sites were identified in 281 prote ...[more]

PMID: 33436009

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Project description:Methicillin-resistant Staphylococcus aureus (MRSA) infection has become a public health crisis. Recently, we isolated small-colony variants (SCVs) of MRSA, which are characterized by slow growth, decreased virulence, increased antibiotic resistance, and immune evasion. In the present study, we provided proteomic and transcriptomic profiles of clinical MRSA sequence type 239 (ST239) normal strains and SCVs and attempted to identify the key genes or pathways closely related to SCV formation and survival. RNAs and proteins were extracted and subjected to RNA sequencing and mass spectrometry, and the transcriptome and proteome were evaluated via bioinformatic analysis. The results were verified by functional assays. In total, 822 differentially expressed genes (DEGs) and 773 differentially expressed proteins (DEPs) were identified; of these, 286 DEGs and DEPs were correlated and subjected to Kyoto Encyclopedia Genes and Genomes analysis. Some pathways were significant, including ABC transporters, ribosome biogenesis, and metabolic pathways such as glycolysis/gluconeogenesis and the citrate cycle (tricarboxylic acid [TCA] cycle). Based on these results, we found that the downregulation of ABC transporters and the TCA cycle pathway resulted in electron transport chain deficiencies and reduced ATP production in SCVs, leading to a dependence on glycolysis and its upregulation. In addition, the upregulation of capsule polysaccharides and the downregulation of surface proteins prevented phagocytosis and reduced the adhesion of host cells, contributing to immune evasion by SCVs. These findings contribute to a better understanding of the mechanisms of SCV formation and survival. IMPORTANCE Small-colony variants (SCVs) of Staphylococcus aureus have drawn increasing research attention. Owing to their slow growth, atypical colony morphology, and unusual metabolic characteristics, SCVs often cause confusion in the laboratory. Furthermore, clinical treatment of SCVs is challenging owing to their antibiotic resistance and immune evasion, leading to persistent and recurrent infections. However, the mechanisms underlying their formation remain unclear. In this study, we isolated SCVs of methicillin-resistant S. aureus and provided transcriptomic and proteomic profiles of normal strains and SCVs. Based on our analysis, glycolysis upregulation and TCA cycle downregulation affected the electron transport chain and energy supply, leading to slower metabolism. Moreover, capsular biosynthesis was increased, while the number of surface proteins decreased, thus promoting immune evasion by SCVs.

Dataset Information

Malonyl-proteome profiles of Staphylococcus aureus reveal lysine malonylation modification in enzymes involved in energy metabolism.

Background

Results

Conclusions

Publications

Malonyl-proteome profiles of Staphylococcus aureus reveal lysine malonylation modification in enzymes involved in energy metabolism.

Similar Datasets

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