ArticleCell host & microbe2022
Thymidine starvation promotes c-di-AMP-dependent inflammation during pathogenic bacterial infection.
Article in Cell host & microbe, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 29 citations in OpenAlex.
- Cyclic di-AMP signaling and regulation inmSphere · 2026Review
- A c-di-AMP-controlled glutamine synthesis pathway promotes persistence ofbioRxiv : the preprint server for biology · 2026Article
- A c-di-AMP receptor mediates epithelial adhesion of Lactiplantibacillus plantarum.Nature communications · 2026Article
- cGAS/STING sensing in dendritic cells discriminates between daptomycin sensitive and resistantiScience · 2026Article
- Targeting cGAS-STING signaling to overcome antibiotic-resistant bacterial infections: Challenges and opportunities.Science advances · 2026Review
- Cyclic di-AMP inhibitsmBio · 2026Article
- Metabolically hijacked Listeria monocytogenes synergizes STING activation and dual cell death for enhanced antitumor immunotherapy.Journal of nanobiotechnology · 2025Article
- Brief exposure to oral antibiotics has age-dependent effects on morphine reward and gene expression in the medial prefrontal cortex of adolescent and adult mice.Brain, behavior, and immunity · 2025Article
- Structural dynamics-guided engineering of a riboswitch RNA for evolving c-di-AMP synthases.Science advances · 2025Article
- The role of the gut microbiota in regulating responses to vaccination: current knowledge and future directions.The FEBS journal · 2025Review
- A Purely Biomanufactured System for Delivering Nanoparticles and STING Agonists.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Article
- Gut Dysbiosis Drives Inflammatory Bowel Disease Through the CCL4L2-VSIR Axis in Glycogen Storage Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Thymidine-dependent Staphylococcus aureus and lung function in patients with cystic fibrosis: a 10-year retrospective case-control study.Jornal brasileiro de pneumologia : publicacao oficial da Sociedade Brasileira de Pneumologia e Tisilogia · 2024Article
- STING trafficking as a new dimension of immune signaling.The Journal of experimental medicine · 2023Article
- Contributions of the microbiota to the systemic inflammatory response.Microbiota and host · 2023Article
- Silver Nanoparticles and Graphene Oxide Complex as an Anti-Inflammatory Biocompatible Liquid Nano-Dressing for Skin Infected withJournal of inflammation research · 2023Article
- Innovative Strategies to Overcome Antimicrobial Resistance and Tolerance.Microorganisms · 2022Review
- The role of bacterial cyclic di-adenosine monophosphate in the host immune response.Frontiers in microbiology · 2022Review
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9 authors at 1 institution in 1 country.
Funding
Abstract
Antimicrobials can impact bacterial physiology and host immunity with negative treatment outcomes. Extensive exposure to antifolate antibiotics promotes thymidine-dependent Staphylococcus aureus small colony variants (TD-SCVs), commonly associated with worse clinical outcomes. We show that antibiotic-mediated disruption of thymidine synthesis promotes elevated levels of the bacterial second messenger cyclic di-AMP (c-di-AMP), consequently inducing host STING activation and inflammation. An initial antibiotic screen in Firmicutes revealed that c-di-AMP production was largely driven by antifolate antibiotics targeting dihydrofolate reductase (DHFR), which promotes folate regeneration required for thymidine biosynthesis. Additionally, TD-SCVs exhibited excessive c-di-AMP production and STING activation in a thymidine-dependent manner. Murine lung infection with TD-SCVs revealed STING-dependent elevation of proinflammatory cytokines, causing higher airway neutrophil infiltration and activation compared with normal-colony S. aureus and hemin-dependent SCVs. Collectively, our results suggest that thymidine metabolism disruption in Firmicutes leads to elevated c-di-AMP-mediated STING-dependent inflammation, with potential impacts on antibiotic usage and infection outcomes.
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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.