Evidence mapPaperPMID 40555231Full record

ArticleCell host & microbe2025

Methylglyoxal is an antibacterial effector produced by macrophages during infection.

Andrea Anaya-Sanchez, Samuel B Berry, Scott Espich, Alex Zilinskas, Phuong M Tran, Carolina Agudelo, Helia Samani, K Heran Darwin, Daniel A Portnoy, Sarah A Stanley

Abstract read
In one paragraph

Article in Cell host & microbe, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
field-weighted citation impact
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

14 citing papers in PubMed.

  1. Article
  2. Methylglyoxal AttenuatesInternational journal of molecular sciences · 2026
    Article
  3. Article
  4. Avoidance of MAIT cells is an essential determinant ofProceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  5. Host methylglyoxal activates theProceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  6. Article
  7. Article
  8. Article
  9. A putativeFrontiers in immunology · 2026
    Article
  10. Cell envelope maintenance by PhoP is essential forProceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  11. Review
  12. Article
  13. Article
  14. Frontiers in bioengineering and biotechnology · 2025
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors.

Andrea Anaya-SanchezMicrobiology Graduate Group, University of California, Berkeley, Berkeley, CA, USA.
Samuel B BerryDivision of Immunology and Molecular Medicine, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA.
Scott EspichDivision of Infectious Disease and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA, USA.
Alex ZilinskasDivision of Immunology and Molecular Medicine, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA.
Phuong M TranDepartment of Microbiology, NYU Grossman School of Medicine, New York, NY, USA.
Carolina AgudeloDivision of Infectious Disease and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA, USA.
Helia SamaniDivision of Immunology and Molecular Medicine, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA.
K Heran DarwinDepartment of Microbiology, NYU Grossman School of Medicine, New York, NY, USA.
Daniel A PortnoyMicrobiology Graduate Group, University of California, Berkeley, Berkeley, CA, USA; Division of Immunology and Molecular Medicine, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA. Electronic address: portnoy@berkeley.edu.
Sarah A StanleyMicrobiology Graduate Group, University of California, Berkeley, Berkeley, CA, USA; Division of Immunology and Molecular Medicine, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA; Division of Infectious Disease and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA, USA. Electronic address: sastanley@berkeley.edu.

Funding

The intersection of innate and adaptive immunity to intracellular pathogensP01AI063302 · UNIVERSITY OF CALIFORNIA BERKELEY · 2004 to 2025
$5.0M
METABOLIC ALDEHYDES AS IMMUNE EFFECTORS AGAINST TUBERCULOSISR01AI153197 · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2025 to 2025
$3.2M
Listeria Hemolysis and Escape From a VacuoleR01AI027655 · UNIVERSITY OF PENNSYLVANIA · 1993 to 2025
$2.5M
Reversing cancer immunosuppression using attenuated Listeria monocytogenesR01CA283604 · UNIVERSITY OF CALIFORNIA BERKELEY · 2025 to 2025
$474k
NCI NIH HHS R01 CA283604NIAID NIH HHS P01 AI063302NIAID NIH HHS R01 AI027655NIAID NIH HHS R01 AI113270NIAID NIH HHS R01 AI153197
6 · The paper itself

Abstract

Infected macrophages transition into aerobic glycolysis, a metabolic program crucial for controlling bacterial infection. However, antimicrobial mechanisms supported by aerobic glycolysis are unclear. Methylglyoxal is a highly toxic aldehyde that modifies proteins and DNA and is produced as a side product of glycolysis. We show that despite this toxicity, infected macrophages generate high levels of methylglyoxal during aerobic glycolysis while downregulating the detoxification system, including glyoxalase 1 (GLO1). Dampening methylglyoxal generation in mice resulted in enhanced survival of Listeria monocytogenes and Mycobacterium tuberculosis, whereas mice lacking Glo1 have increased methylglyoxal levels and improved infection control. Furthermore, bacteria unable to detoxify methylglyoxal (ΔgloA) exhibit attenuated virulence but are partially rescued in mice that cannot enter glycolysis and generate methylglyoxal. This loss of bacterial GloA results in up to a 1,000-fold greater genomic mutation frequency during infection. Collectively, these results suggest that methylglyoxal is an antimicrobial innate effector that defends against bacterial pathogens.

Indexed as

Anti-Bacterial AgentsListeria monocytogenesMacrophagesMycobacterium tuberculosisPyruvaldehydeAnimalsGlycolysisLactoylglutathione LyaseListeriosisMiceMice, Inbred C57BLVirulenceAnti-Bacterial AgentsLactoylglutathione LyasePyruvaldehydebacterial pathogensglycolysisinnate immunitymethylglyoxal

Identifiers

PMID40555231
PMCPMC12245573

What Socratic holds

Textmetadata
LicenceTDM
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 Socratic graph.