Evidence map›Paper›PMID 36801104›Full record

ArticleEBioMedicine2023

A broad-spectrum synthetic antibiotic that does not evoke bacterial resistance.

Douglas M Heithoff, Scott P Mahan, Lucien Barnes V, Semen A Leyn, Cyril X George, Jaime E Zlamal, Jakkarin Limwongyut, Guillermo C Bazan, Jeffrey C Fried, Lynn N Fitzgibbons and 5 more

Open access · goldFull text read
PubMed Full text at PMC Publisher
In one paragraph

Article in EBioMedicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed, 1 pooled it
2.4field-weighted citation impact, top 10% 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

11 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 citations in OpenAlex.

  1. Pooled it
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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

15 authors at 4 institutions in 2 countries.

Douglas M HeithoffDepartment of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, CA, 93106, USA; Institute for Collaborative Biotechnologies, University of California, Santa Barbara, CA, 93106, USA.
Scott P MahanDepartment of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, CA, 93106, USA; Institute for Collaborative Biotechnologies, University of California, Santa Barbara, CA, 93106, USA; Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, CA, 95616, USA.
Lucien Barnes VDepartment of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, CA, 93106, USA; Institute for Collaborative Biotechnologies, University of California, Santa Barbara, CA, 93106, USA.
Semen A LeynInfectious and Inflammatory Diseases Research Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, 92037, USA.
Cyril X GeorgeDepartment of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, CA, 93106, USA; Institute for Collaborative Biotechnologies, University of California, Santa Barbara, CA, 93106, USA.
Jaime E ZlamalInfectious and Inflammatory Diseases Research Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, 92037, USA.
Jakkarin LimwongyutInstitute for Collaborative Biotechnologies, University of California, Santa Barbara, CA, 93106, USA; Center for Polymers and Organic Solids, Department of Chemistry and Biochemistry, University of California, Santa Barbara, CA, 93106, USA.
Guillermo C BazanInstitute for Collaborative Biotechnologies, University of California, Santa Barbara, CA, 93106, USA; Center for Polymers and Organic Solids, Department of Chemistry and Biochemistry, University of California, Santa Barbara, CA, 93106, USA; Department of Chemistry, National University of Singapore, 117543, Singapore.
Jeffrey C FriedDepartment of Medical Education, Santa Barbara Cottage Hospital, Santa Barbara, CA, 93105, USA; Department of Pulmonary and Critical Care Medicine, Santa Barbara Cottage Hospital, Santa Barbara, CA, 93105, USA.
Lynn N FitzgibbonsDepartment of Medical Education, Santa Barbara Cottage Hospital, Santa Barbara, CA, 93105, USA; Division of Infectious Diseases, Santa Barbara Cottage Hospital, Santa Barbara, CA, 93105, USA.
John K HouseFaculty of Science, Sydney School of Veterinary Science, The University of Sydney, Camden, New South Wales, 2570, Australia.
Charles E SamuelDepartment of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, CA, 93106, USA; Institute for Collaborative Biotechnologies, University of California, Santa Barbara, CA, 93106, USA.
Andrei L OstermanInfectious and Inflammatory Diseases Research Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, 92037, USA.
David A LowDepartment of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, CA, 93106, USA; Institute for Collaborative Biotechnologies, University of California, Santa Barbara, CA, 93106, USA. Electronic address: dlow@ucsb.edu.
Michael J MahanDepartment of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, CA, 93106, USA; Institute for Collaborative Biotechnologies, University of California, Santa Barbara, CA, 93106, USA. Electronic address: mahan@ucsb.edu.
University of California, Santa Barbara · USDiscovery Institute · USSanta Barbara Cottage Hospital · USThe University of Sydney · AU

Funding

Protein Glycosylation in the Coagulopathy and Inflammation of SepsisP01HL131474 · NHLBI · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI MAHAN, MICHAEL J · 2016 to 2025
$26.2M
Comparative resistomics of Gram-negative bacterial pathogensR01AI167977 · NIAID · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI ANDREI L OSTERMAN · 2022 to 2026
$3.7M
NHLBI NIH HHS P01 HL131474NIAID NIH HHS R01 AI167977
6 · The paper itself

Abstract

backgroundAntimicrobial resistance (AMR) poses a critical threat to public health and disproportionately affects the health and well-being of persons in low-income and middle-income countries. Our aim was to identify synthetic antimicrobials termed conjugated oligoelectrolytes (COEs) that effectively treated AMR infections and whose structures could be readily modified to address current and anticipated patient needs.

methodsFifteen chemical variants were synthesized that contain specific alterations to the COE modular structure, and each variant was evaluated for broad-spectrum antibacterial activity and for in vitro cytotoxicity in cultured mammalian cells. Antibiotic efficacy was analyzed in murine models of sepsis; in vivo toxicity was evaluated via a blinded study of mouse clinical signs as an outcome of drug treatment.

findingsWe identified a compound, COE2-2hexyl, that displayed broad-spectrum antibacterial activity. This compound cured mice infected with clinical bacterial isolates derived from patients with refractory bacteremia and did not evoke bacterial resistance. COE2-2hexyl has specific effects on multiple membrane-associated functions (e.g., septation, motility, ATP synthesis, respiration, membrane permeability to small molecules) that may act together to negate bacterial cell viability and the evolution of drug-resistance. Disruption of these bacterial properties may occur through alteration of critical protein-protein or protein-lipid membrane interfaces-a mechanism of action distinct from many membrane disrupting antimicrobials or detergents that destabilize membranes to induce bacterial cell lysis.

interpretationThe ease of molecular design, synthesis and modular nature of COEs offer many advantages over conventional antimicrobials, making synthesis simple, scalable and affordable. These COE features enable the construction of a spectrum of compounds with the potential for development as a new versatile therapy for an imminent global health crisis.

fundingU.S. Army Research Office, National Institute of Allergy and Infectious Diseases, and National Heart, Lung, and Blood Institute.

Indexed as

Anti-Infective AgentsBacterial InfectionsSepsisAnimalsAnti-Bacterial AgentsBacteriaDrug Resistance, Multiple, BacterialMammalsMiceMicrobial Sensitivity TestsAnti-Bacterial AgentsAnti-Infective AgentsAntibioticsAntimicrobial resistanceCOEConjugated oligoelectrolytesMultidrug-resistant pathogens

Identifiers

PMID36801104
PMCPMC10025758
OpenAlexW4320888629

What Socratic holds

Textfull text, public
LicenceCC BY
reference markers read2
measurements read79
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.