Controlling Recombination to Evolve Bacteriophages DOI Creative Commons
James J. Bull, Holly A. Wichman,

Stephen M. Krone

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(7), P. 585 - 585

Published: March 28, 2024

Recombination among different phages sometimes facilitates their ability to grow on new hosts. Protocols direct the evolution of phage host range, as might be used in application therapy, would then benefit from including steps enable recombination. Applying mathematical and computational models, addition experiments using T3 T7, we consider ways that a protocol may influence recombination levels. We first address coinfection, which is step enabling The multiplicity infection (MOI, ratio cell concentration) insufficient for predicting (co)infection force (the rate at cells are infected) also critical but more challenging measure. Using both high MOI (>1) ensures levels coinfection. apply four-genetic-locus model study effects recombinant Recombinants accumulate over multiple generations growth, less so if one outgrows other. Supplementing pool with low-fitness recovers some this 'lost' Overall, fine tuning rates will not practical wild phages, qualitative enhancement can attained basic procedures.

Language: Английский

Targeting Pseudomonas aeruginosa biofilm with an evolutionary trained bacteriophage cocktail exploiting phage resistance trade-offs DOI Creative Commons

Fabian Kunisch,

Claudia Campobasso, Jeroen Wagemans

et al.

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

Published: Oct. 3, 2024

Language: Английский

Citations

9
More extinction driven by the Red Queen in smaller habitats DOI

Xiao Liu,

Quan‐Guo Zhang

Ecology, Journal Year: 2025, Volume and Issue: 106(2)

Published: Feb. 1, 2025

Populations in antagonistic coevolutionary interactions may "run or die," and their fates are determined by evolutionary potential. The asymmetry of speed between coevolving partners, for example, resulting from genetic constraints, can be mitigated larger populations. We therefore hypothesize more frequent extinction driven coevolution with declining habitat size. In bacterium-virus systems, viruses (the consumers) typically suffer an disadvantage due to constraints variation; this pattern apply host-parasite general. Here, our experiment the bacterium Pseudomonas fluorescens SBW25 its lytic phage virus SBW25Φ2, likelihood viral was greater smaller habitats. Among populations that did persist, those small habitats showed lower infectivity bacterial had densities. Therefore, impact size reduction on biodiversity could exacerbated processes. Our results also lead a number suggestions biocontrol practices, particularly training phages.

Language: Английский

Citations

1
An overview of the current state of phage therapy for the treatment of biofilm-related infections DOI Creative Commons
Diana P. Pires, Luciana Meneses, Ana Brandão

et al.

Current Opinion in Virology, Journal Year: 2022, Volume and Issue: 53, P. 101209 - 101209

Published: Feb. 28, 2022

Bacterial biofilms are involved in many chronic and difficult-to-treat infections. Phage therapy against infectious is becoming a promising strategy, as suggested by the increasing number of publications demonstrating efficacy phages vitro formed biofilms. However, translation between results to vivo phage outcome not straightforward due complexity phage-biofilm interactions clinical contexts. Here, we provide critical overview studies for biofilm control pathogens, followed major outcomes lessons learned from recently reported case (between 2018 2021) biofilm-related

Language: Английский

Citations

36
Phage engineering and phage‐assisted CRISPR‐Cas delivery to combat multidrug‐resistant pathogens DOI Creative Commons

Khushal Khambhati,

Gargi Bhattacharjee, Nisarg Gohil

et al.

Bioengineering & Translational Medicine, Journal Year: 2022, Volume and Issue: 8(2)

Published: Aug. 3, 2022

Antibiotic resistance ranks among the top threats to humanity. Due frequent use of antibiotics, society is facing a high prevalence multidrug resistant pathogens, which have managed evolve mechanisms that help them evade last line therapeutics. An alternative antibiotics could involve bacteriophages (phages), are natural predators bacterial cells. In earlier times, phages were implemented as therapeutic agents for century but mainly replaced with and considering menace antimicrobial resistance, it might again become interest due increasing threat antibiotic pathogens. The current understanding phage biology clustered regularly interspaced short palindromic repeats (CRISPR) assisted genome engineering techniques facilitated generate variants unique values. this review, we briefly explain strategies engineer bacteriophages. Next, highlight literature supporting CRISPR-Cas9-assisted effective more specific targeting Lastly, discuss either increase fitness, specificity, or lytic ability control an infection.

Language: Английский

Citations

36
Phage therapy for pulmonary infections: lessons from clinical experiences and key considerations DOI Creative Commons
Georgia Mitropoulou, Angela Koutsokera, Chantal Csajka

et al.

European Respiratory Review, Journal Year: 2022, Volume and Issue: 31(166), P. 220121 - 220121

Published: Oct. 5, 2022

Lower respiratory tract infections lead to significant morbidity and mortality. They are increasingly caused by multidrug-resistant pathogens, notably in individuals with cystic fibrosis, hospital-acquired pneumonia lung transplantation. The use of bacteriophages (phages) treat bacterial is gaining growing attention, numerous published cases compassionate treatment over the last few years. Although phages appears safe, lack standardisation, heterogeneity studies paucity robust efficacy data, alongside regulatory hurdles arising from existing pharmaceutical legislation, just some challenges phage therapy has overcome. In this review, we discuss lessons learned recent clinical experiences for pulmonary infections. We review key aspects, opportunities regarding formulations administration routes, interactions antibiotics immune system, resistance. Building upon current knowledge base, future pre-clinical using emerging technologies carefully designed trials expected enhance our understanding explore therapeutic potential therapy.

Language: Английский

Citations

35
Development of an Anti-Acinetobacter baumannii Biofilm Phage Cocktail: Genomic Adaptation to the Host DOI
Lucía Blasco, Inés Bleriot, Manuel González de Aledo

et al.

Antimicrobial Agents and Chemotherapy, Journal Year: 2022, Volume and Issue: 66(3)

Published: Jan. 18, 2022

The need for alternatives to antibiotic therapy due the emergence of multidrug resistant bacteria (MDR), such as nosocomial pathogen Acinetobacter baumannii, has led recovery phage therapy. In addition, phages can be combined in cocktails increase host range. this study, evolutionary mechanism adaptation was utilized order develop a adapted A. named Ab105-2phiΔCI404ad, from mutant lytic phage, Ab105-2phiΔCI, previously developed by our group. whole genome sequence Ab105-2phiΔCI404ad determined, showing that four genomic rearrangements events occurred tail morphogenesis module affecting ORFs encoding receptor binding sites. As consequence rearrangements, 10 were lost and new obtained, all proteins; two inverted regions also derived these events. process increased range almost 3-fold. depolymerase-expressing phenotype, indicated formation halo, which not observed ancestral obtained 81% infected strains. A cocktail formed combining with baumannii vB_AbaP_B3, known express depolymerase. Both individual showed strong antimicrobial activity against 5 clinical strains 1 reference strain tested. However, cases resistance bacterial observed. antibiofilm assayed. displayed activity.

Language: Английский

Citations

29
Understanding the Mechanisms That Drive Phage Resistance in Staphylococci to Prevent Phage Therapy Failure DOI Creative Commons
Andrea Jurado, Lucía Fernández, Ana Rodrı́guez

et al.

Viruses, Journal Year: 2022, Volume and Issue: 14(5), P. 1061 - 1061

Published: May 16, 2022

Despite occurring at the microscopic scale, armed race between phages and their bacterial hosts involves multiple mechanisms, some of which are just starting to be understood. On one hand, bacteria have evolved strategies that can stop viral infection different stages (adsorption, DNA injection replication, biosynthesis assembly progeny and/or release newly formed virions); on other, gradually counterattack allow them continue infecting prey. This co-evolutionary process has played a major role in development microbial populations both natural man-made environments. Notably, understanding parameters this war will paramount fully benefit from application phage therapy against dangerous, antibiotic-resistant human pathogens. review gathers current knowledge regarding mechanisms resistance Staphylococcus genus, includes aureus, most concerning microorganisms terms antibiotic acquisition. Some these involve permanent changes cell via mutations, while others transient, adaptive whose expression depends certain environmental cues or growth phase. Finally, we discuss plausible limit impact therapy, with special emphasis importance rational design cocktails order thwart therapeutic failure.

Language: Английский

Citations

29
The dynamic interplay of bacteriophage, bacteria and the mammalian host during phage therapy DOI Creative Commons
Jacopo Marchi, Sophia Zborowsky, Laurent Debarbieux

et al.

iScience, Journal Year: 2023, Volume and Issue: 26(2), P. 106004 - 106004

Published: Jan. 18, 2023

For decades, biomedically centered studies of bacteria have focused on mechanistic drivers disease in their mammalian hosts. Likewise, molecular bacteriophage understanding mechanisms by which exploit the intracellular environment bacterial These binary interactions – infect and eukaryotic hosts remained largely separate lines inquiry. However, recent evidence demonstrates how tripartite between bacteriophage, host shape dynamics fate each component. In this perspective, we provide an overview different ways ecology modulates infections along a spectrum positive to negative impacts host. We also examine coevolutionary processes over longer timescales may change valence these interactions. argue that anticipating both ecological evolutionary is key understand control ultimately success or failure phage therapy.

Language: Английский

Citations

21
Case Studies in the Assessment of Microbial Fitness: Seemingly Subtle Changes Can Have Major Effects on Phenotypic Outcomes DOI Creative Commons
Sarah B. Worthan,

Robert D. P. McCarthy,

Megan G. Behringer

et al.

Journal of Molecular Evolution, Journal Year: 2023, Volume and Issue: 91(3), P. 311 - 324

Published: Feb. 8, 2023

Abstract Following the completion of an adaptive evolution experiment, fitness evaluations are routinely conducted to assess magnitude adaptation. In doing so, proper consideration should be given when determining appropriate methods as trade-offs may exist between accuracy and throughput. Here, we present three instances in which small changes framework or execution significantly impacted outcomes. The first case illustrates that discrepancies conclusions can arise depending on approach evaluating fitness, culture vessel used, sampling method. second reveals variations environmental conditions occur associated with material. Specifically, these subtle greatly affect microbial physiology leading pH distorting measurements. Finally, last reports heterogeneity CFU formation time result inaccurate conclusions. Based each case, considerations recommendations presented for future experiments.

Language: Английский

Citations

17
Engineering Phages to Fight Multidrug-Resistant Bacteria DOI Creative Commons
Huan Peng, Irene A. Chen, Udi Qimron

et al.

Chemical Reviews, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 16, 2024

Facing the global "superbug" crisis due to emergence and selection for antibiotic resistance, phages are among most promising solutions. Fighting multidrug-resistant bacteria requires precise diagnosis of bacterial pathogens specific cell-killing. Phages have several potential advantages over conventional antibacterial agents such as host specificity, self-amplification, easy production, low toxicity well biofilm degradation. However, narrow range, uncharacterized properties, risks from exponential replication evolution natural phages, currently limit their applications. Engineering can not only enhance range improve phage efficacy, but also confer new functions. This review first summarizes major engineering techniques including both chemical modification genetic engineering. Subsequent sections discuss applications engineered pathogen detection ablation through interdisciplinary approaches synthetic biology nanotechnology. We future directions persistent challenges in ongoing exploration control.

Language: Английский

Citations

8