Evidence map›Paper›PMID 40901883›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2025

Resurfacing promotes antibacterial activity of a lipid A-binding nanobody.

Angela C O'Donnell, Xun Wang, Nikol Kadeřábková, Kyra E Groover, Bethany C Perez, Amanda Helms, Jennifer S Brodbelt, Despoina A I Mavridou, Bryan W Davies

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Monoclonal Antibodies Targeting Bacterial Infections: A Broad Review of the Field.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026
    Review
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

9 authors.

Angela C O'DonnellDepartment of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712.ORCID 0000-0003-1408-5431
Xun WangDepartment of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712.
Nikol KadeřábkováDepartment of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712.ORCID 0000-0002-1205-1644
Kyra E GrooverDepartment of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712.ORCID 0000-0001-6755-820X
Bethany C PerezDepartment of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712.ORCID 0009-0005-4809-3618
Amanda HelmsDepartment of Chemistry, The University of Texas at Austin, Austin, TX 78712.
Jennifer S BrodbeltDepartment of Chemistry, The University of Texas at Austin, Austin, TX 78712.ORCID 0000-0003-3207-0217
Despoina A I MavridouDepartment of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712.ORCID 0000-0002-7449-1151
Bryan W DaviesDepartment of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712.ORCID 0000-0002-2046-0341

Funding

Investigating nanobodies to target multidrug resistant bacterial pathogensR01AI148419 · NIAID · UNIVERSITY OF TEXAS AT AUSTIN · PI DAVIES, BRYAN WILLIAM · 2020 to 2023
$2.8M
Vibrio microcins. A hidden field of targeted anti-cholerae natural products.R01AI182365 · NIAID · UNIVERSITY OF TEXAS AT AUSTIN · PI Bryan William Davies · 2024 to 2026
$2.2M
The interplay between cell envelope protein homeostasis and antibiotic resistance in Gram-negative bacteriaR01AI158753 · NIAID · UNIVERSITY OF TEXAS AT AUSTIN · PI Despoina Mavridou · 2022 to 2026
$1.9M
From microcin sequence to function: linking sequence variation to antimicrobial activityR56AI179799 · NIAID · UNIVERSITY OF TEXAS AT AUSTIN · PI DAVIES, BRYAN WILLIAM · 2024 to 2024
$726k
HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID) R01AI158753HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID) R56 AI179199NIAID NIH HHS R01 AI148419NIAID NIH HHS R01 AI158753NIAID NIH HHS R01 AI182365NIAID NIH HHS R56 AI179799Texas Biologics TXB-24-02)Welch Foundation (The Welch Foundation) F-2137
6 · The paper itself

Abstract

Nanobodies have been pursued as candidates for antimicrobial design due to their small size and versatile binding capacities, but direct antibacterial activity of a nanobody has yet to be described. Here, we employed a bacterial surface display platform to screen a synthetic library of nanobody variants for antimicrobial potential. We identified a candidate that binds the essential lipid A component of gram-negative lipopolysaccharide. Nonetheless, this nanobody required a weakened outer membrane to access its target and elicit its toxic activity. Borrowing from observations of innate immune proteins, we found that resurfacing nanobodies with positively charged residues enabled them to bind and perturb the gram-negative outer membrane, but this alone was not sufficient for toxic activity. However, when we resurface our lipid A-targeting nanobody, it gained the ability to disrupt the outer membrane and enact its antibacterial function against wild-type bacteria. This development of a dual-function nanobody that can reach and bind previously inaccessible gram-negative targets introduces a route for antimicrobial biologic advancement.

Indexed as

Anti-Bacterial AgentsLipid ASingle-Domain AntibodiesProtein BindingAnti-Bacterial AgentsLipid ASingle-Domain Antibodiesantibacteriallipid Amembrane disruptionnanobodyresurfacing

Identifiers

PMID40901883
PMCPMC12435215

What OpenQuestion holds

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LicenceCC BY
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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.