Evidence map›Paper›PMID 32241895›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2020

Synthetic molecular evolution of host cell-compatible, antimicrobial peptides effective against drug-resistant, biofilm-forming bacteria.

Charles G Starr, Jenisha Ghimire, Shantanu Guha, Joseph P Hoffmann, Yihui Wang, Leisheng Sun, Brooke N Landreneau, Zachary D Kolansky, Isabella M Kilanowski-Doroh, Mimi C Sammarco and 2 more

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed
6.0field-weighted citation impact, top 3% 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

38 citing papers in PubMed, 68 citations in OpenAlex.

  1. Review
  2. The Evolution of Symbiosis inBiomolecules · 2026
    Review
  3. Killing of colistin-resistantMicrobiology spectrum · 2025
    Article
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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

12 authors at 1 institution in 1 country.

Charles G StarrDepartment of Biochemistry and Molecular Biology, Tulane University School of Medicine, New Orleans, LA 70112.
Jenisha GhimireDepartment of Biochemistry and Molecular Biology, Tulane University School of Medicine, New Orleans, LA 70112.ORCID 0000-0002-3097-4194
Shantanu GuhaDepartment of Biochemistry and Molecular Biology, Tulane University School of Medicine, New Orleans, LA 70112.
Joseph P HoffmannDepartment of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, LA 70112.
Yihui WangDepartment of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, LA 70112.
Leisheng SunDepartment of Biochemistry and Molecular Biology, Tulane University School of Medicine, New Orleans, LA 70112.ORCID 0000-0003-0358-1421
Brooke N LandreneauDepartment of Biochemistry and Molecular Biology, Tulane University School of Medicine, New Orleans, LA 70112.
Zachary D KolanskyDepartment of Biochemistry and Molecular Biology, Tulane University School of Medicine, New Orleans, LA 70112.
Isabella M Kilanowski-DorohDepartment of Biochemistry and Molecular Biology, Tulane University School of Medicine, New Orleans, LA 70112.ORCID 0000-0003-4998-8171
Mimi C SammarcoDepartment of Surgery, Tulane University School of Medicine, New Orleans, LA 70112.
Lisa A MoriciDepartment of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, LA 70112.ORCID 0000-0002-4799-4941
William C WimleyDepartment of Biochemistry and Molecular Biology, Tulane University School of Medicine, New Orleans, LA 70112; wwimley@tulane.edu.
Tulane University · US

Funding

Tracking & Evaluation CoreU54GM104940 · NIGMS · LSU PENNINGTON BIOMEDICAL RESEARCH CTR · PI JUDD E SHELLITO · 2012 to 2026
$69.1M
Molecular evolution of Peptide antibiotics for drug-resistant Gram negative bacteriaR21AI119104 · NIAID · TULANE UNIVERSITY OF LOUISIANA · PI WIMLEY, WILLIAM C · 2015 to 2016
$405k
NIAID NIH HHS R21 AI119104NIGMS NIH HHS U54 GM104940
6 · The paper itself

Abstract

Novel classes of antibiotics and new strategies to prevent and treat infections are urgently needed because the rapid rise in drug-resistant bacterial infections in recent decades has been accompanied by a parallel decline in development of new antibiotics. Membrane permeabilizing antimicrobial peptides (AMPs) have long been considered a potentially promising, novel class of antibiotic, especially for wound protection and treatment to prevent the development of serious infections. Yet, despite thousands of known examples, AMPs have only infrequently proceeded as far as clinical trials, especially the chemically simple, linear examples. In part, this is due to impediments that often limit their applications in vivo. These can include low solubility, residual toxicity, susceptibility to proteolysis, and loss of activity due to host cell, tissue, and protein binding. Here we show how synthetic molecular evolution can be used to evolve potentially advantageous antimicrobial peptides that lack these impediments from parent peptides that have at least some of them. As an example of how the antibiotic discovery pipeline can be populated with more promising candidates, we evolved and optimized one family of linear AMPs into a new generation with high solubility, low cytotoxicity, potent broad-spectrum sterilizing activity against a panel of gram-positive and gram-negative ESKAPE pathogens, and antibiofilm activity against gram-positive and gram-negative biofilms. The evolved peptides have these activities in vitro even in the presence of concentrated host cells and also in vivo in the complex, cell- and protein-rich environment of a purulent animal wound model infected with drug-resistant bacteria.

Indexed as

Drug Resistance, BacterialAnimalsAnti-Bacterial AgentsAntimicrobial Cationic PeptidesBacteriaBacterial InfectionsBiofilmsDirected Molecular EvolutionFemaleHumansMiceMicrobial Sensitivity TestsAnti-Bacterial AgentsAntimicrobial Cationic Peptidesantimicrobial peptidedrug resistant bacteriaMRSAPseudomonaswound care

Identifiers

PMID32241895
PMCPMC7165445
OpenAlexW3015152499

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.