Evidence map›Paper›PMID 27672085›Full record

ArticleInfection and immunity2016

The Bacterial Second Messenger Cyclic di-GMP Regulates Brucella Pathogenesis and Leads to Altered Host Immune Response.

Mike Khan, Jerome S Harms, Fernanda M Marim, Leah Armon, Cherisse L Hall, Yi-Ping Liu, Menachem Banai, Sergio C Oliveira, Gary A Splitter, Judith A Smith

Open access · bronzeAbstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
3.1field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

23 citing papers in PubMed, 29 citations in OpenAlex.

  1. Review
  2. Deletion of the c-di-GMP Phosphodiesterase BpdB AttenuatesInternational journal of molecular sciences · 2026
    Article
  3. Article
  4. Review
  5. Article
  6. Article
  7. Review
  8. TheAnnual review of microbiology · 2023
    Review
  9. Frontiers in microbiology · 2023
    Article
  10. Review
  11. Review
  12. Microorganisms · 2021
    Review
  13. Uncovering the Hidden Credentials ofMicrobiology and molecular biology reviews : MMBR · 2021
    Review
  14. STING Contributes to Host Defense AgainstFrontiers in immunology · 2021
    Article
  15. Doxycycline Induces Apoptosis ofFrontiers in cellular and infection microbiology · 2021
    Article
  16. Article
  17. Proteomics of Brucella.Proteomes · 2020
    Review
  18. Article
  19. Journal of immunology (Baltimore, Md. : 1950) · 2018
    Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 3 institutions in 3 countries.

Mike KhanCellular and Molecular Pathology Training Program, University of Wisconsin-Madison, Madison, Wisconsin, USA mkhan23@wisc.edu.
Jerome S HarmsDepartment of Pathobiological Sciences, University of Wisconsin-Madison School of Veterinary Medicine, Madison, Wisconsin, USA.
Fernanda M MarimDepartamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte-Minas Gerais, Brazil.
Leah ArmonMina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.
Cherisse L HallDepartment of Pediatrics, University of Wisconsin-Madison School of Medicine and Public Health, Madison, Wisconsin, USA.
Yi-Ping LiuDepartment of Pediatrics, University of Wisconsin-Madison School of Medicine and Public Health, Madison, Wisconsin, USA.
Menachem BanaiDepartment of Bacteriology, Kimron Veterinary Institute, Beit Dagan, Israel.
Sergio C OliveiraDepartamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte-Minas Gerais, Brazil.
Gary A SplitterDepartment of Pathobiological Sciences, University of Wisconsin-Madison School of Veterinary Medicine, Madison, Wisconsin, USA.
Judith A SmithDepartment of Pediatrics, University of Wisconsin-Madison School of Medicine and Public Health, Madison, Wisconsin, USA.
University of Wisconsin–Madison · USUniversidade Federal de Minas Gerais · BRBar-Ilan University · IL

Funding

Brucella epitope recognition by CD8+ T cellsR01AI073558 · NIAID · UNIVERSITY OF WISCONSIN-MADISON · PI HARMS, JEROME SCOTT, SMITH, JUDITH ANNE · 2008 to 2016
$3.3M
Brucella survival strategy requires endoplasmic reticulum restructuring and interferes with innate immunityR01AI116453 · NIAID · FOUNDATION FOR RESEARCH DEVELOPMENT · PI BARBER, GLEN N, OLIVEIRA, SERGIO C · 2016 to 2025
$1.4M
The role of the Unfolded Protein Response in Brucella melitensis replicationF31AI115931 · NIAID · UNIVERSITY OF WISCONSIN-MADISON · PI KHAN, MIKE · 2015 to 2017
$93k
NIAID NIH HHS F31 AI115931NIAID NIH HHS R01 AI073558NIAID NIH HHS R01 AI116453
6 · The paper itself

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.

Indexed as

Adaptation, PhysiologicalAnimalsBiofilmsBrucellaBrucellosisCells, CulturedCyclic GMPGenetic FitnessMacrophagesMembrane ProteinsMiceMice, Inbred BALB CMice, Inbred C57BLMice, KnockoutMutationSTING Proteinbis(3',5')-cyclic diguanylic acidCyclic GMPMembrane ProteinsSting1 protein, mouseSTING ProteinType IV Secretion Systems

Identifiers

PMID27672085
PMCPMC5116723
OpenAlexW2526466832

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.