Evidence map›Paper›PMID 40333180›Full record

ArticleCell reports2025

Bactericidal activity of mammalian histones is caused by large membrane pore formation.

Leora Duong, Yonghan Wu, Summer J Kasallis, Serena Abbondante, Paul J Hurst, Michaela E Marshall, Katherine McCarthy, Babu J N Reddy, Jean-Louis Bru, Kumar Perinbam and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed.

  1. Geometric ordering in bacterial communities.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  2. Article
  3. Chromatin-derived histone proteins fromFrontiers in cellular and infection microbiology · 2026
    Article
  4. Frontiers in microbiology · 2026
    Article
  5. Review
  6. 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

14 authors.

Leora DuongDepartment of Molecular Biology and Biochemistry, University of California, Irvine, Irvine, CA 92697, USA.
Yonghan WuDepartment of Physics and Astronomy, University of California, Irvine, Irvine, CA 92697, USA.
Summer J KasallisDepartment of Physics and Astronomy, University of California, Irvine, Irvine, CA 92697, USA.
Serena AbbondanteDepartment of Ophthalmology, University of California, Irvine, Irvine, CA 92697, USA; Department of Physiology and Biophysics, University of California, Irvine, Irvine, CA 92697, USA.
Paul J HurstDepartment of Chemistry, University of California, Irvine, Irvine, CA 92697, USA.
Michaela E MarshallDepartment of Ophthalmology, University of California, Irvine, Irvine, CA 92697, USA; Department of Physiology and Biophysics, University of California, Irvine, Irvine, CA 92697, USA.
Katherine McCarthyDepartment of Molecular Biology and Biochemistry, University of California, Irvine, Irvine, CA 92697, USA.
Babu J N ReddyDepartment of Developmental and Cell Biology, University of California, Irvine, Irvine, CA 92697, USA.
Jean-Louis BruDepartment of Molecular Biology and Biochemistry, University of California, Irvine, Irvine, CA 92697, USA.
Kumar PerinbamDepartment of Physics and Astronomy, University of California, Irvine, Irvine, CA 92697, USA; School of Basic and Applied Sciences, Dayananda Sagar University, Bengaluru, Karnataka 560078, India.
Eric PearlmanDepartment of Ophthalmology, University of California, Irvine, Irvine, CA 92697, USA; Department of Physiology and Biophysics, University of California, Irvine, Irvine, CA 92697, USA.
Joseph P PattersonDepartment of Chemistry, University of California, Irvine, Irvine, CA 92697, USA.
Steven P GrossDepartment of Physics and Astronomy, University of California, Irvine, Irvine, CA 92697, USA; Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA 92697, USA. Electronic address: sgross@uci.edu.
Albert SiryapornDepartment of Molecular Biology and Biochemistry, University of California, Irvine, Irvine, CA 92697, USA; Department of Physics and Astronomy, University of California, Irvine, Irvine, CA 92697, USA. Electronic address: asirya@uci.edu.

Funding

Synergistic killing of bacterial pathogens by histonesR01AI163196 · NIAID · UNIVERSITY OF CALIFORNIA-IRVINE · PI Albert Siryaporn · 2022 to 2026
$2.5M
NIAID NIH HHS R01 AI163196
6 · The paper itself

Abstract

Histones have an important role in eukaryotic innate immunity, wherein histones co-localize with antimicrobial peptides (AMPs). The mechanism of histone cooperation with AMPs and the extent to which histones form pores both remain a mystery. Here, we show that histones form large pores in bacterial membranes that lack lipopolysaccharide (LPS) and that their antimicrobial effect is significantly stronger than that of the clinical AMP polymyxin B. We find that histones and AMPs together produce potent antimicrobial synergy through the formation of 26 nm pores, whereby the pore-forming activity of AMPs on LPS-containing membranes enables histones to enter the periplasmic space and subsequently attack unprotected membranes to create pores. We provide a mechanistic explanation for the long-standing observations of histone antimicrobial activity and demonstrate how antimicrobial synergy arises. The ubiquity of histones and AMPs in innate immunity has significant implications for organismal defense and can be leveraged for novel antibiotic strategies.

Indexed as

Anti-Bacterial AgentsAntimicrobial PeptidesCell MembraneHistonesAnimalsAntimicrobial Cationic PeptidesEscherichia coliHumansImmunity, InnateLipopolysaccharidesPolymyxin BAnti-Bacterial AgentsAntimicrobial Cationic PeptidesAntimicrobial PeptidesHistonesLipopolysaccharidesPolymyxin Bantibioticsantimicrobial peptidesantimicrobial synergybacterial membrane porescolistinCP: Microbiologyhistonesinnate immunitylipopolysaccharidepolymyxinpore formation

Identifiers

PMID40333180
PMCPMC12168145

What Socratic holds

Textmetadata
LicenceCC BY
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.