ArticleInfection and immunity2016
The Bacterial Second Messenger Cyclic di-GMP Regulates Brucella Pathogenesis and Leads to Altered Host Immune Response.
Article in Infection and immunity, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
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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
23 citing papers in PubMed, 29 citations in OpenAlex.
- Review
- Deletion of the c-di-GMP Phosphodiesterase BpdB AttenuatesInternational journal of molecular sciences · 2026Article
- IFI204-STING drives protective innate immunity against gangrenousFrontiers in immunology · 2026Article
- Damage-associated molecular patterns (DAMPs) in diseases: implications for therapy.Molecular biomedicine · 2025Review
- STING contributes to the inflammation and proliferation ofInfection and immunity · 2025Article
- The role of cyclic di-GMP in biomaterial-associated infections caused by commensal Escherichia coli.PloS one · 2025Article
- STING-Pathway Inhibiting Nanoparticles (SPINs) as a Platform for Treatment of Inflammatory Diseases.ACS applied bio materials · 2024Review
- TheAnnual review of microbiology · 2023Review
- Article
- Multifaceted functions of STING in human health and disease: from molecular mechanism to targeted strategy.Signal transduction and targeted therapy · 2022Review
- Activation of mucosal immunity as a novel therapeutic strategy for combating brucellosis.Frontiers in microbiology · 2022Review
- Review
- Uncovering the Hidden Credentials ofMicrobiology and molecular biology reviews : MMBR · 2021Review
- STING Contributes to Host Defense AgainstFrontiers in immunology · 2021Article
- Doxycycline Induces Apoptosis ofFrontiers in cellular and infection microbiology · 2021Article
- Brucella suppress STING expression via miR-24 to enhance infection.PLoS pathogens · 2020Article
- Proteomics of Brucella.Proteomes · 2020Review
- Brucella Peptide Cross-Reactive Major Histocompatibility Complex Class I Presentation Activates SIINFEKL-Specific T Cell Receptor-Expressing T Cells.Infection and immunity · 2018Article
- Article
- Genomic analysis of the original Elberg Brucella melitensis Rev.1 vaccine strain reveals insights into virulence attenuation.Virulence · 2018Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 3 countries.
Funding
Abstract
Brucella species are facultative intracellular bacteria that cause brucellosis, a chronic debilitating disease significantly impacting global health and prosperity. Much remains to be learned about how Brucella spp. succeed in sabotaging immune host cells and how Brucella spp. respond to environmental challenges. Multiple types of bacteria employ the prokaryotic second messenger cyclic di-GMP (c-di-GMP) to coordinate responses to shifting environments. To determine the role of c-di-GMP in Brucella physiology and in shaping host-Brucella interactions, we utilized c-di-GMP regulatory enzyme deletion mutants. Our results show that a ΔbpdA phosphodiesterase mutant producing excess c-di-GMP displays marked attenuation in vitro and in vivo during later infections. Although c-di-GMP is known to stimulate the innate sensor STING, surprisingly, the ΔbpdA mutant induced a weaker host immune response than did wild-type Brucella or the low-c-di-GMP guanylate cyclase ΔcgsB mutant. Proteomics analysis revealed that c-di-GMP regulates several processes critical for virulence, including cell wall and biofilm formation, nutrient acquisition, and the type IV secretion system. Finally, ΔbpdA mutants exhibited altered morphology and were hypersensitive to nutrient-limiting conditions. In summary, our results indicate a vital role for c-di-GMP in allowing Brucella to successfully navigate stressful and shifting environments to establish intracellular infection.
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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.