ArticleCell host & microbe2017
A Lipoylated Metabolic Protein Released by Staphylococcus aureus Suppresses Macrophage Activation.
Article in Cell host & microbe, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 50 citations in OpenAlex.
- Bacterial lipid structural diversity mediates commensalism and pathogenesis.Nature reviews. Microbiology · 2026Review
- Immune protection and persistence in Pseudomonas aeruginosa infections by pyruvate cross-feeding.Nature communications · 2026Article
- The cellular esterase FrmB controls metabolic homeostasis and small colony variant formation inbioRxiv : the preprint server for biology · 2026Article
- Staphylococcus aureus exploits lipoic acid salvage to combat host oxidative stress.Cell reports · 2025Article
- Signal Peptides: From Molecular Mechanisms to Applications in Protein and Vaccine Engineering.Biomolecules · 2025Review
- Gram-positive pathogens, inflammation, and the host lipid environment.Current opinion in microbiology · 2025Review
- Bacterial single-cell RNA sequencing captures biofilm transcriptional heterogeneity and differential responses to immune pressure.Nature communications · 2024Article
- Conserved moonlighting protein pyruvate dehydrogenase induces robust protection againstProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Substrate Analogues Entering the Lipoic Acid Salvage Pathway via Lipoate-Protein Ligase 2 Interfere withACS infectious diseases · 2024Article
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- Chemical and biomolecular insights into theIsrael journal of chemistry · 2023Article
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- Characterization of MroQ-Dependent Maturation and Export of the Staphylococcus aureus Accessory Gene Regulatory System Autoinducing Peptide.Infection and immunity · 2022Article
- Extracellular fibrinogen-binding protein released by intracellular Staphylococcus aureus suppresses host immunity by targeting TRAF3.Nature communications · 2022Article
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- Neutrophil extracellular traps enhance macrophage killing of bacterial pathogens.Science advances · 2021Article
- Branched chain fatty acid synthesis drives tissue-specific innate immune response and infection dynamics of Staphylococcus aureus.PLoS pathogens · 2021Article
- Interplay between Yersinia pestis and its flea vector in lipoate metabolism.The ISME journal · 2021Article
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4 authors at 1 institution in 1 country.
Funding
Abstract
The virulence factors of pathogenic microbes often have single functions that permit immune suppression. However, a proportion possess multiple activities and are considered moonlighting proteins. By examining secreted virulence factors of Staphylococcus aureus, we determine that the bacterial lipoic acid synthetase LipA suppresses macrophage activation. LipA is known to modify the E2 subunit of the metabolic enzyme complex pyruvate dehydrogenase (E2-PDH) with a fatty acid derivative, lipoic acid, yielding the metabolic protein lipoyl-E2-PDH. We demonstrate that lipoyl-E2-PDH is also released by S. aureus and moonlights as a macrophage immunosuppressant by reducing Toll-like receptor 1/2 (TLR1/2) activation by bacterial lipopeptides. A LipA-deficient strain induces heightened pro-inflammatory cytokine production, which is diminished in the absence of TLR2. During murine systemic infection, LipA suppresses pro-inflammatory macrophage activation, rendering these cells inefficient at controlling infection. These observations suggest that bacterial metabolism and immune evasion are linked by virtue of this moonlighting protein.
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