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Comparison of bacterial suppression by phage cocktails, dual-receptor generalists, and coevolutionarily trained phages.

作者信息

Borin Joshua M, Lee Justin J, Gerbino Krista R, Meyer Justin R

机构信息

Division of Biological Sciences University of California San Diego La Jolla California USA.

出版信息

Evol Appl. 2022 Dec 9;16(1):152-162. doi: 10.1111/eva.13518. eCollection 2023 Jan.


DOI:10.1111/eva.13518
PMID:36699129
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9850009/
Abstract

The evolution and spread of antibiotic-resistant bacteria have renewed interest in phage therapy, the use of bacterial viruses (phages) to combat bacterial infections. The delivery of phages in cocktails where constituent phages target different modalities (e.g., receptors) may improve treatment outcomes by making it more difficult for bacteria to evolve resistance. However, the multipartite nature of cocktails may lead to unintended evolutionary and ecological outcomes. Here, we compare a 2-phage cocktail with a largely unconsidered group of phages: generalists that can infect through multiple, independent receptors. We find that λ phage generalists and cocktails that target the same receptors (LamB and OmpF) suppress similarly for ~2 days. Yet, a "trained" generalist phage, which previously adapted to its host via 28 days of coevolution, demonstrated superior suppression. To understand why the trained generalist was more effective, we measured the resistance of bacteria against each of our phages. We find that, when bacteria were assailed by two phages in the cocktail, they evolved mutations in , a host inner-membrane transporter that λ uses to move its DNA across the periplasmic space and into the cell for infection. This provided cross-resistance against the cocktail and untrained generalist. However, these mutations were ineffective at blocking the trained generalist because, through coevolutionary training, it evolved to bypass resistance. The trained generalist's past experiences in training make it exceedingly difficult for bacteria to evolve resistance, further demonstrating the utility of coevolutionary phage training for improving the therapeutic properties of phages.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a98b/9850009/40c588cf8ee2/EVA-16-152-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a98b/9850009/49a457d3c806/EVA-16-152-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a98b/9850009/87104361542d/EVA-16-152-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a98b/9850009/972292a93dc8/EVA-16-152-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a98b/9850009/d59c3af8d150/EVA-16-152-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a98b/9850009/ac0febe17864/EVA-16-152-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a98b/9850009/40c588cf8ee2/EVA-16-152-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a98b/9850009/49a457d3c806/EVA-16-152-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a98b/9850009/87104361542d/EVA-16-152-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a98b/9850009/972292a93dc8/EVA-16-152-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a98b/9850009/d59c3af8d150/EVA-16-152-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a98b/9850009/ac0febe17864/EVA-16-152-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a98b/9850009/40c588cf8ee2/EVA-16-152-g003.jpg

相似文献

[1]
Comparison of bacterial suppression by phage cocktails, dual-receptor generalists, and coevolutionarily trained phages.

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引用本文的文献

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Phage Therapy: Combating Evolution of Bacterial Resistance to Phages.

Viruses. 2025-8-8

[2]
Current Clinical Laboratory Challenges to Widespread Adoption of Phage Therapy in the United States.

Antibiotics (Basel). 2025-5-29

[3]
Non-antibiotic therapies for multidrug-resistant gastrointestinal infections: an overview of the use of probiotics, natural compounds, and bacteriophages.

Front Antibiot. 2025-5-6

[4]
Isolation, characterization, and application of the novel polyvalent bacteriophage vB_EcoM_XAM237 against pathogenic Escherichia coli.

Vet Res. 2025-4-24

[5]
Can Bacteriophages Be Effectively Utilized for Disinfection in Animal-Derived Food Products? A Systematic Review.

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[6]
Phage Therapy for : Overcoming Challenges, Unleashing Potential.

Infect Dis Rep. 2025-3-12

[7]
Bacteriophage therapy for multidrug-resistant infections: current technologies and therapeutic approaches.

J Clin Invest. 2025-3-3

[8]
Factors Affecting Phage-Bacteria Coevolution Dynamics.

Viruses. 2025-2-8

[9]
Multi-strain phage induced clearance of bacterial infections.

PLoS Comput Biol. 2025-2-4

[10]
Inferring strain-level mutational drivers of phage-bacteria interaction phenotypes arising during coevolutionary dynamics.

Virus Evol. 2024-11-29

本文引用的文献

[1]
Host-parasite coevolution promotes innovation through deformations in fitness landscapes.

Elife. 2022-7-6

[2]
Phage Therapy of Mycobacterium Infections: Compassionate Use of Phages in 20 Patients With Drug-Resistant Mycobacterial Disease.

Clin Infect Dis. 2023-1-6

[3]
Viral protein instability enhances host-range evolvability.

PLoS Genet. 2022-2

[4]
Leapfrog dynamics in phage-bacteria coevolution revealed by joint analysis of cross-infection phenotypes and whole genome sequencing.

Ecol Lett. 2022-4

[5]
Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis.

Lancet. 2022-2-12

[6]
Functional diversity increases the efficacy of phage combinations.

Microbiology (Reading). 2021-12

[7]
Phage Cocktail Development for Bacteriophage Therapy: Toward Improving Spectrum of Activity Breadth and Depth.

Pharmaceuticals (Basel). 2021-10-3

[8]
Coevolutionary phage training leads to greater bacterial suppression and delays the evolution of phage resistance.

Proc Natl Acad Sci U S A. 2021-6-8

[9]
Sustained coevolution of phage Lambda and involves inner- as well as outer-membrane defences and counter-defences.

Microbiology (Reading). 2021-5

[10]
Unlocking the next generation of phage therapy: the key is in the receptors.

Curr Opin Biotechnol. 2021-4

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