ArticleProceedings of the National Academy of Sciences of the United States of America2013
Exchange protein directly activated by cAMP plays a critical role in bacterial invasion during fatal rickettsioses.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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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
53 citing papers in PubMed, 84 citations in OpenAlex.
- In vitro screening of the open-access Pandemic Response Box reveals ESI-09 as a compound with activity against Echinococcus multilocularis.International journal for parasitology. Drugs and drug resistance · 2025Article
- Role of exchange proteins directly activated by cAMP signaling in vascular remodeling.Pharmacological reviews · 2025Review
- Phosphatidylserine-binding receptor, CD300f, on macrophages mediates host invasion of pathogenic and non-pathogenic rickettsiae.Infection and immunity · 2025Article
- Integrative study of lung cancer adeno-to-squamous transition in EGFR TKI resistance identifies RAPGEF3 as a therapeutic target.National science review · 2024Article
- Annexin A2: A Double-Edged Sword in Pathogen Infection.Pathogens (Basel, Switzerland) · 2024Review
- Article
- Innate immunity in rickettsial infections.Frontiers in cellular and infection microbiology · 2023Review
- Epac1 activation by cAMP regulates cellular SUMOylation and promotes the formation of biomolecular condensates.Science advances · 2022Article
- Intracellular receptor EPAC regulates von Willebrand factor secretion from endothelial cells in a PI3K-/eNOS-dependent manner during inflammation.The Journal of biological chemistry · 2021Article
- Article
- Host EPAC1 Modulates Rickettsial Adhesion to Vascular Endothelial Cells via Regulation of ANXA2 Y23 Phosphorylation.Pathogens (Basel, Switzerland) · 2021Article
- Cells within cells: Rickettsiales and the obligate intracellular bacterial lifestyle.Nature reviews. Microbiology · 2021Review
- Article
- Cell-Type Apoptosis in Lung during SARS-CoV-2 Infection.Pathogens (Basel, Switzerland) · 2021Article
- Anti-cancer strategy targeting the energy metabolism of tumor cells surviving a low-nutrient acidic microenvironment.Molecular metabolism · 2020Article
- Review
- Increased talin-vinculin spatial proximities in livers in response to spotted fever group rickettsial and Ebola virus infections.Laboratory investigation; a journal of technical methods and pathology · 2020Article
- Annexin A2 depletion exacerbates the intracerebral microhemorrhage induced by acute rickettsia and Ebola virus infections.PLoS neglected tropical diseases · 2020Article
- Recent research milestones in the pathogenesis of human rickettsioses and opportunities ahead.Future microbiology · 2020Review
- Targeting the Small GTPase Superfamily through Their Regulatory Proteins.Angewandte Chemie (International ed. in English) · 2020Review
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
Abstract
Rickettsiae are responsible for some of the most devastating human infections. A high infectivity and severe illness after inhalation make some rickettsiae bioterrorism threats. We report that deletion of the exchange protein directly activated by cAMP (Epac) gene, Epac1, in mice protects them from an ordinarily lethal dose of rickettsiae. Inhibition of Epac1 suppresses bacterial adhesion and invasion. Most importantly, pharmacological inhibition of Epac1 in vivo using an Epac-specific small-molecule inhibitor, ESI-09, completely recapitulates the Epac1 knockout phenotype. ESI-09 treatment dramatically decreases the morbidity and mortality associated with fatal spotted fever rickettsiosis. Our results demonstrate that Epac1-mediated signaling represents a mechanism for host-pathogen interactions and that Epac1 is a potential target for the prevention and treatment of fatal rickettsioses.
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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.