ArticlePLoS pathogens2021
Branched chain fatty acid synthesis drives tissue-specific innate immune response and infection dynamics of Staphylococcus aureus.
Article in PLoS pathogens, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 25 citations in OpenAlex.
- Bacterial lipid structural diversity mediates commensalism and pathogenesis.Nature reviews. Microbiology · 2026Review
- Staphylococcus aureus adapts to the host nutritional environment by coordinating the activity of central metabolic enzymes.PLoS pathogens · 2026Article
- The cellular esterase FrmB controls metabolic homeostasis and small colony variant formation inbioRxiv : the preprint server for biology · 2026Article
- Integrated Phenotypic and Transcriptomic Analyses Unveil the Antibacterial Mechanism of Punicalagin Against Methicillin-ResistantFoods (Basel, Switzerland) · 2025Article
- Isoleucine Binding and Regulation ofBiochemistry · 2025Article
- The Three-Dimensional Structure of the Genome of the Dark Septate EndophyteJournal of fungi (Basel, Switzerland) · 2025Article
- Gram-positive pathogens, inflammation, and the host lipid environment.Current opinion in microbiology · 2025Review
- Bacterial acquisition of host fatty acids has far-reaching implications on virulence.Microbiology and molecular biology reviews : MMBR · 2024Review
- Quantifying acyl-chain diversity in isobaric compound lipids containing monomethyl branched-chain fatty acids.bioRxiv : the preprint server for biology · 2024Article
- Lipase-mediated detoxification of host-derived antimicrobial fatty acids by Staphylococcus aureus.Communications biology · 2024Article
- Growth ofbioRxiv : the preprint server for biology · 2024Article
- The Acari Hypothesis, VI: human sebum and the cutaneous microbiome in allergy and in lipid homeostasis.Frontiers in allergy · 2024Article
- Lipase and Protease Production Ability of Multi-drug Resistant Bacteria Worsens the Outcomes of Wound Infections.Current pharmaceutical design · 2024Article
- Article
- GehB Inactivates Lipoproteins to Delay the Healing of Acute Wounds Infected with Staphylococcus aureus.Current microbiology · 2023Article
- Microbial Volatiles as Diagnostic Biomarkers of Bacterial Lung Infection in Mechanically Ventilated Patients.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2023Article
- Immunometabolites Drive Bacterial Adaptation to the Airway.Frontiers in immunology · 2021Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Fatty acid-derived acyl chains of phospholipids and lipoproteins are central to bacterial membrane fluidity and lipoprotein function. Though it can incorporate exogenous unsaturated fatty acids (UFA), Staphylococcus aureus synthesizes branched chain fatty acids (BCFA), not UFA, to modulate or increase membrane fluidity. However, both endogenous BCFA and exogenous UFA can be attached to bacterial lipoproteins. Furthermore, S. aureus membrane lipid content varies based upon the amount of exogenous lipid in the environment. Thus far, the relevance of acyl chain diversity within the S. aureus cell envelope is limited to the observation that attachment of UFA to lipoproteins enhances cytokine secretion by cell lines in a TLR2-dependent manner. Here, we leveraged a BCFA auxotroph of S. aureus and determined that driving UFA incorporation disrupted infection dynamics and increased cytokine production in the liver during systemic infection of mice. In contrast, infection of TLR2-deficient mice restored inflammatory cytokines and bacterial burden to wildtype levels, linking the shift in acyl chain composition toward UFA to detrimental immune activation in vivo. In in vitro studies, bacterial lipoproteins isolated from UFA-supplemented cultures were resistant to lipase-mediated ester hydrolysis and exhibited heightened TLR2-dependent innate cell activation, whereas lipoproteins with BCFA esters were completely inactivated after lipase treatment. These results suggest that de novo synthesis of BCFA reduces lipoprotein-mediated TLR2 activation and improves lipase-mediated hydrolysis making it an important determinant of innate immunity. Overall, this study highlights the potential relevance of cell envelope acyl chain repertoire in infection dynamics of bacterial pathogens.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.