Drivers and consequences of bacteriophage host range

FEMS Microbiology Reviews, Journal Year: 2023, Volume and Issue: 47(4)

Published: July 1, 2023

Abstract Bacteriophages are obligate parasites of bacteria characterized by the breadth hosts that they can infect. This “host range” depends on genotypes and morphologies phage bacterial host, but also environment in which interacting. Understanding host range is critical to predicting impacts these their natural communities utility as therapeutic agents, key how phages evolve doing so drive evolutionary change populations, including through movement genes among unrelated genomes. Here, we explore drivers infection from molecular underpinnings phage–host interaction ecological context occur. We further evaluate importance intrinsic, transient, environmental shaping replication, discuss each influences over time. The has great consequences phage-based application strategies, well community dynamics, therefore highlight both recent developments open questions field therapeutics come back into focus.

Language: Английский

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Bacteriophage DNA induces an interrupted immune response during phage therapy in a chicken model

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: March 13, 2024

One of the hopes for overcoming antibiotic resistance crisis is use bacteriophages to combat bacterial infections, so-called phage therapy. This therapeutic approach generally believed be safe humans and animals as phages should infect only prokaryotic cells. Nevertheless, recent studies suggested that might recognized by eukaryotic cells, inducing specific cellular responses. Here we show in chickens infected with Salmonella enterica treated a cocktail, are initially animal cells viruses, however, cGAS-STING pathway (one two major pathways innate antiviral response) blocked at stage IRF3 transcription factor phosphorylation. inhibition due inability RNA polymerase III recognize DNA produce dsRNA molecules which necessary stimulate large protein complex indispensable phosphorylation, indicating mechanism response impairment.

Language: Английский

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Use of Bacteriophages to Target Intracellular Pathogens

Clinical Infectious Diseases, Journal Year: 2023, Volume and Issue: 77(Supplement_5), P. S423 - S432

Published: Nov. 1, 2023

Abstract Bacteriophages (phages) have shown great potential as natural antimicrobials against extracellular pathogens (eg, Escherichia coli or Klebsiella pneumoniae), but little is known about how they interact with intracellular targets Shigella spp., Salmonella Mycobacterium spp.) in the mammalian host. Recent research has demonstrated that phages can enter human cells. However, for design of successful clinical applications, further investigation required to define their subcellular behavior and understand complex biological processes underlie interaction bacterial targets. In this review, we summarize molecular evidence phage internalization eucaryotic cells, specific focus on proof activity within host, current proposed strategies overcome poor penetrance issues may impact therapeutic use most clinically relevant pathogens.

Language: Английский

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Transcytosis of T4 Bacteriophage Through Intestinal Cells Enhances Its Immune Activation

Viruses, Journal Year: 2025, Volume and Issue: 17(1), P. 134 - 134

Published: Jan. 19, 2025

Interactions between bacteriophages with mammalian immune cells are of great interest and most phages possess at least one molecular pattern (nucleic acid, sugar residue, or protein structure) that is recognizable to the system through pathogen associated (PAMP) receptors (i.e., TLRs). Given reside in same body niches as bacteria, they share propensity stimulate quench responses depending on nature their interactions host cells. While vitro research focuses outcomes direct application interest, potential impact transcytosis intestinal barrier has yet be considered. As a necessary step healthy systems for access by phage underlying cell populations, it imperative understand how this may play role activation. We compared activation macrophages (as measured TNFα secretion) following those stimulated incubation transcytosed polarized Caco2 epithelial model. Our results demonstrate capable activating secretion upon contact maintain stimulatory capability transcytosis. Furthermore, enhanced occurring an equivalent multiplicity directly applied phage.

Language: Английский

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Multi-strain phage induced clearance of bacterial infections

PLoS Computational Biology, Journal Year: 2025, Volume and Issue: 21(2), P. e1012793 - e1012793

Published: Feb. 4, 2025

Bacteriophage (or ‘phage’ – viruses that infect and kill bacteria) are increasingly considered as a therapeutic alternative to treat antibiotic-resistant bacterial infections. However, bacteria can evolve resistance phage, presenting significant challenge the near- long-term success of phage therapeutics. Application mixtures multiple phages ( i.e. , ‘cocktails’) has been proposed limit emergence phage-resistant mutants could lead failure. Here, we combine theory computational models in vivo therapy study efficacy cocktail, composed two complementary motivated by example Pseudomonas aeruginosa facing exploit different surface receptors, LUZ19v PAK_P1. As confirmed Luria-Delbr�ck fluctuation test, this motivating serves model for instances where extremely unlikely develop simultaneous mutations against both phages. We then quantify outcomes given single- or double-phage treatment models, function traits host immune strength. Building upon prior work showing monophage immunocompetent hosts, here show cocktails comprised targeting independent receptors improve outcome immunocompromised hosts reduce chance pathogens simultaneously combinations. The finding cocktail is qualitatively robust differences virus-bacteria interactions dynamics. Altogether, combined use analysis highlights influence viral life history receptor complementarity when designing deploying hosts.

Language: Английский

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Urinary bacteriophage cooperation with bacterial pathogens during human urinary tract infections supports lysogenic phage therapy

Communications Biology, Journal Year: 2025, Volume and Issue: 8(1)

Published: Feb. 4, 2025

Despite much promise in overcoming drug-resistant infections, clinical studies of bacteriophage antibacterial therapy have failed to show durable effectiveness. Although lysogeny plays an important role bacterial physiology, its significance diverse microbiomes remains unclear. Here, we tested the following hypotheses: 1) urinary microbiome phage populations switch a higher relative proportion temperate phages, and 2) activity recombination machinery (integration/excision/transposition) is during human tract infections (UTIs) than non-infected tracts. Using urine, model organisms, mass spectrometry, gene expression analysis, phenotype prediction BACPHLIP, results corroborated our hypotheses at functional protein levels. From health perspective, these data suggest that phages may facilitate rather function as protective agents. These findings support use lysogenic therapeutic Trojan Horses. During enriched with increased activity, possibly facilitating infections. Temperate could be used "Trojan Horses".

Language: Английский

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vB_Ent31 Bacteriophage May Combat Enterobacter cloacae Infections with Macrophage Modulating Activity

Virology, Journal Year: 2025, Volume and Issue: 605, P. 110463 - 110463

Published: Feb. 25, 2025

Language: Английский

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Innovative strategies in the fight against bacterial infections: Phage therapy, nanotechnology, and new antimicrobial agents for multidrug-resistant pathogens

Results in Chemistry, Journal Year: 2025, Volume and Issue: unknown, P. 102304 - 102304

Published: April 1, 2025

Language: Английский

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Tracking tripartite interaction dynamics: isolation, integration, and influence of bacteriophages in the Paraburkholderia-Dictyostelium discoideum symbiosis system

Frontiers in Microbiology, Journal Year: 2025, Volume and Issue: 16

Published: May 2, 2025

Introduction Bacteriophages influence interactions between bacterial symbionts and their hosts by exerting parasitic pressure on symbiont populations facilitating evolution through selection, gene exchange, prophage integration. Host organisms also modulate phage-bacteria interactions, with host-specific contexts potentially limiting or promoting phage access to driving alternative phenotypic evolutionary outcomes. Methods To better elucidate tripartite phage-bacteria-host in real-time, we expanded the Dictyostelium discoideum-Paraburkholderia symbiosis system include Paraburkholderia -specific phages. We isolated six environmental phages from soil samples using a multi-host enrichment approach. identified functional monocultures of one strains implemented These were evaluated across all three amoeba-associated species. Finally, treated infected amoeba lines select isolates assessed effects prevalence host fitness. Results The exhibited diverse plaquing characteristics virion morphologies, collectively targeting belonging each amoeba-symbiotic Following treatment experiments, observed that application some cases reduced infection alleviated fitness impacts, while others, no significant noted. Notably, able persist within symbiont-infected over multiple culture transfers, indicating potential long-term interactions. Discussion findings highlight variability phage-symbiont environment underscore complex nature lays foundation for future studies exploring dynamics systems, suggesting mechanisms may shape differential outcomes presenting valuable avenues investigation.

Language: Английский

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Macrophage-induced reduction of bacteriophage density limits the efficacy ofin vivopulmonary phage therapy

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 16, 2024

Abstract The rise of antimicrobial resistance has led to renewed interest in evaluating phage therapy. In murine models highly effective treatment acute pneumonia caused by Pseudomonas aeruginosa relies on the synergistic antibacterial activity bacteriophages with neutrophils. Here, we show that depletion alveolar macrophages (AM) shortens survival mice without boosting P. load lungs. Unexpectedly, upon bacteriophage treatment, pulmonary levels were significantly lower AM-depleted than immunocompetent mice. To explore potential mechanisms underlying benefit AM-depletion treated mice, developed a mathematical model phage, bacteria, and innate immune system dynamics. Simulations from fitted data suggest AM reduce density We experimentally confirmed vivo decay is faster compared animals. These findings demonstrate involvement feedback between bacteriophage, shaping outcomes therapy clinical settings.

Language: Английский

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