Evidence map›Paper›PMID 40027640›Full record

ArticlebioRxiv : the preprint server for biology2025

Chemical inhibition of a bacterial immune system 1.

Zhiyu Zang, Olivia K Duncan, Dziugas Sabonis, Yun Shi, Gause Miraj, Iana Fedorova, Shuai Le, Jun Deng, Yuhao Zhu, Yanyao Cai and 8 more

Abstract readPreprint
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors.

Zhiyu ZangDepartment of Chemistry, Indiana University, Bloomington, IN 47405, USA.
Olivia K DuncanDepartment of Chemistry, Indiana University, Bloomington, IN 47405, USA.
Dziugas SabonisInstitute of Biotechnology, Life Sciences Center, Vilnius University, Vilnius, Lithuania.
Yun ShiInstitute for Biomedicine and Glycomics, Griffith University, Gold Coast, QLD, Australia.
Gause MirajInstitute for Biomedicine and Glycomics, Griffith University, Gold Coast, QLD, Australia.
Iana FedorovaDepartment of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, 94158, USA.
Shuai LeDepartment of Microbiology, College of Basic Medical Sciences, Key Laboratory of Microbial Engineering Committee in Chongqing, Army Medical University, Chongqing, 400038, China.
Jun DengDepartment of Microbiology, College of Basic Medical Sciences, Key Laboratory of Microbial Engineering Committee in Chongqing, Army Medical University, Chongqing, 400038, China.
Yuhao ZhuDepartment of Microbiology, College of Basic Medical Sciences, Key Laboratory of Microbial Engineering Committee in Chongqing, Army Medical University, Chongqing, 400038, China.
Yanyao CaiDepartment of Chemistry, Indiana University, Bloomington, IN 47405, USA.
Chengqian ZhangDepartment of Chemistry, Indiana University, Bloomington, IN 47405, USA.
Garima AryaDepartment of Immunology and Microbiology, University of Colorado Anschutz Medical Campus, School of Medicine, Aurora, CO 80045, USA.
Breck A DuerkopDepartment of Immunology and Microbiology, University of Colorado Anschutz Medical Campus, School of Medicine, Aurora, CO 80045, USA.
Haihua LiangCollege of Medicine, Southern University of Science and Technology, Shenzhen, China.
Joseph Bondy-DenomyDepartment of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, 94158, USA.
Thomas VeInstitute for Biomedicine and Glycomics, Griffith University, Gold Coast, QLD, Australia.
Giedre TamulaitieneInstitute of Biotechnology, Life Sciences Center, Vilnius University, Vilnius, Lithuania.
Joseph P GerdtDepartment of Chemistry, Indiana University, Bloomington, IN 47405, USA.ORCID 0000-0002-0375-4110

Funding

Mechanistic basis of bacteriophages for the decolonization of vancomycin resistant enterococci in the intestine.R01AI141479 · NIAID · UNIVERSITY OF COLORADO DENVER · PI DUERKOP, BRECK A · 2018 to 2025
$4.4M
NRSA Training CoreTL1TR002531 · NCATS · INDIANA UNIVERSITY INDIANAPOLIS · PI FOTI, DANIEL JUSTIN, HURLEY, THOMAS D. · 2018 to 2022
$2.5M
NCATS NIH HHS TL1 TR002531NIAID NIH HHS R01 AI141479
6 · The paper itself

Abstract

The rise of antibiotic resistance motivates a revived interest in phage therapy. However, bacteria possess dozens of anti-bacteriophage immune systems that confer resistance to therapeutic phages. Chemical inhibitors of these anti-phage immune systems could be employed as adjuvants to overcome resistance in phage-based therapies. Here, we report that anti-phage systems can be selectively inhibited by small molecules, thereby sensitizing phage-resistant bacteria to phages. We discovered a class of chemical inhibitors that inhibit the type II Thoeris anti-phage immune system. These inhibitors block the biosynthesis of a histidine-ADPR intracellular 'alarm' signal by ThsB and prevent ThsA from arresting phage replication. These inhibitors promiscuously inhibit type II Thoeris systems from diverse bacteria-including antibiotic-resistant pathogens. Chemical inhibition of the Thoeris defense improved the efficacy of a model phage therapy against a phage-resistant strain of

Identifiers

PMID40027640
PMCPMC11870472

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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.