ArticleNature microbiology2020
Lactate production by Staphylococcus aureus biofilm inhibits HDAC11 to reprogramme the host immune response during persistent infection.
Article in Nature microbiology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 147 papers, 2 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
147 citing papers in PubMed, 2 syntheses or guidelines pooled it, 237 citations in OpenAlex.
- The evolving landscape ofFrontiers in immunology · 2026Pooled it
- Single-cell transcriptome reveals Staphylococcus aureus modulating fibroblast differentiation in the bone-implant interface.Molecular medicine (Cambridge, Mass.) · 2023Pooled it
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- Osteomyelitis: Epidemiology, Classification, Pathophysiology, Clinical Features, Diagnosis, and Management.MedComm · 2026Review
- Reversing Macrophage Immunometabolic Dysfunction in Prolonged Infections Via a Glutaminolysis-Fueled Restoration-Based Hierarchically Selective Therapeutic System.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
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- Protein lactylation in health and diseases: molecular mechanisms, biological significance, and clinical implications.Signal transduction and targeted therapy · 2026Review
- Synergistic tissue destruction byBiofilm · 2026Article
- Reduced Oxygen Condition Is Associated with Genome-Wide Expression Changes in Mastitis-LineageInternational journal of molecular sciences · 2026Article
- Hdac11 promotes idiopathic pulmonary fibrosis through macrophage M2-type polarization and myofibroblast accumulation by inhibiting Parkin-dependent mitophagy.Nature communications · 2026Article
- Mitochondrial transfer to granulocytic myeloid-derived suppressor cells augments immunosuppressive activity.Cell reports · 2026Article
- Differential sensitivity of leukocyte populations toInfection and immunity · 2026Article
- Prolactin and 17β-Estradiol Are Epigenetic Regulators That Modify the Effector Response of Bovine Macrophages DuringMicroorganisms · 2026Article
- An Enzyme-Like Catalyzed Nanosheets for Redox Stress Oscillation Therapy Against Bacterial Infections.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Glutamate nanoregulator for metabolic immunotherapy of biofilm-associated implant infections.Journal of nanobiotechnology · 2026Article
- Methicillin-resistant and susceptible Staphylococcus aureus: tolerance, immune evasion and treatment.Nature reviews. Microbiology · 2026Review
- Emerging non-antibiotic strategies for implant-associated biofilm infections by reprogramming the dysregulated immune microenvironment.NPJ biofilms and microbiomes · 2026Review
- How do immunometabolites shape bacterial infections?PLoS biology · 2026Article
- Functional biomaterials for the treatment of periprosthetic joint infection: A systematic review of preclinical animal studies.Journal of orthopaedic translation · 2026Review
87 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 6 institutions in 1 country.
Funding
Abstract
Staphylococcus aureus is a leading cause of biofilm-associated prosthetic joint infection (PJI), resulting in considerable disability and prolonged treatment. It is known that host leukocyte IL-10 production is required for S. aureus biofilm persistence in PJI. An S. aureus bursa aurealis Tn library consisting of 1,952 non-essential genes was screened for mutants that failed to induce IL-10 in myeloid-derived suppressor cells (MDSCs), which identified a critical role for bacterial lactic acid biosynthesis. We generated an S. aureus ddh/ldh1/ldh2 triple Tn mutant that cannot produce D- or L-lactate. Co-culture of MDSCs or macrophages with ddh/ldh1/ldh2 mutant biofilm produced substantially less IL-10 compared with wild-type S. aureus, which was also observed in a mouse model of PJI and led to reduced biofilm burden. Using MDSCs recovered from the mouse PJI model and in vitro leukocyte-biofilm co-cultures, we show that bacterial-derived lactate inhibits histone deacetylase 11, causing unchecked HDAC6 activity and increased histone 3 acetylation at the Il-10 promoter, resulting in enhanced Il-10 transcription in MDSCs and macrophages. Finally, we show that synovial fluid of patients with PJI contains elevated amounts of D-lactate and IL-10 compared with control subjects, and bacterial lactate increases IL-10 production by human monocyte-derived macrophages.
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Registered trials
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.