A tale of two phage tails: Engineering the host range of bacteriophages infectingClostridioides difficile DOI Creative Commons

Joanna P. Steczynska,

S. J. Kerr,

Michelle L. Kelly

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Oct. 17, 2023

Abstract Clostridioides difficile infection (CDI) is a leading cause of antibiotic-associated diarrhoea across the globe. Although treatable with restricted number antibiotics, emergence resistant variants and high relapse rates necessitate alternative countermeasures. Phage therapy represents an attractive option. However, its implementation handicapped by narrow host specificity C. bacteriophages isolated to date. One strategy rationally expand phage range would be make appropriate modifications receptor binding protein (RBP). Here, we identify tail fibre as RBP two Myoviridae phages, ΦCD1801 ΦCD2301, which were previously propagated using strains CD1801 (RT078) CD2301 (RT014), respectively. Contrary studies into reprogramming ranges other bacterial species, exchanging genes ( tcf/tfp ) alone between was insufficient change specificity. Rather, alterations dependent their exchange together putative chaperone encoded hyp , localised adjacent gene. Capitalising on this discovery, CRISPR/Cas9 used one that swapping respective genes. Significantly, resulting mutants, surpassed both parental phages in terms efficiency infection. This first time genome engineering has successfully expanded phage, prerequisite for implementing treatment CDI. Importance Alternatives antibiotics treating are urgently required. presents option it potential clear minimal microbiome disruption eliminate possibility recurrence. date have highly ranges. Moreover, rational strategies alter till now been precluded identity proteins involved largely unknown. demonstrated associated determine phage. enabled alteration through CRISPR-mediated editing creation derivative exceeding phages. engineering.

Language: Английский

Fecal microbiota transplantation: current challenges and future landscapes DOI
Abbas Yadegar, Haggai Bar‐Yoseph, Tanya Monaghan

et al.

Clinical Microbiology Reviews, Journal Year: 2024, Volume and Issue: 37(2)

Published: May 8, 2024

SUMMARYGiven the importance of gut microbial homeostasis in maintaining health, there has been considerable interest developing innovative therapeutic strategies for restoring microbiota. One such approach, fecal microbiota transplantation (FMT), is main "whole microbiome replacement" strategy and integrated into clinical practice guidelines treating recurrent

Language: Английский

Citations

49
The gut virome is associated with stress-induced changes in behaviour and immune responses in mice DOI Creative Commons
Nathaniel L. Ritz, Lorraine A. Draper, Thomaz F. S. Bastiaanssen

et al.

Nature Microbiology, Journal Year: 2024, Volume and Issue: 9(2), P. 359 - 376

Published: Feb. 5, 2024

The microbiota-gut-brain axis has been shown to play an important role in the stress response, but previous work focused primarily on of bacteriome. gut virome constitutes a major portion microbiome, with bacteriophages having potential remodel bacteriome structure and activity. Here we use mouse model chronic social stress, employ 16S rRNA whole metagenomic sequencing faecal pellets determine how is modulated by contributes effects stress. We found that led behavioural, immune alterations mice were associated changes bacteriophage class Caudoviricetes unassigned viral taxa. To whether these causally related stress-associated behavioural or physiological outcomes, conducted transplant from before autochthonously transferred it undergoing transfer protected against behaviour sequelae restored stress-induced select circulating cell populations, cytokine release, gene expression amygdala. These data provide evidence plays modulation during indicating populations should be considered when designing future microbiome-directed therapies.

Language: Английский

Citations

34
The Next Generation Fecal Microbiota Transplantation: To Transplant Bacteria or Virome DOI Creative Commons

You Yu,

Weihong Wang, Faming Zhang

et al.

Advanced Science, Journal Year: 2023, Volume and Issue: 10(35)

Published: Nov. 1, 2023

Abstract Fecal microbiota transplantation (FMT) has emerged as a promising therapeutic approach for dysbiosis‐related diseases. However, the clinical practice of crude fecal transplants presents limitations in terms acceptability and reproductivity. Consequently, two alternative solutions to FMT are developed: transplanting bacteria communities or virome. Advanced methods mainly include washed spores treatment. Transplanting virome is also explored, with development transplantation, which involves filtering from feces. These approaches provide more palatable options patients healthcare providers while minimizing research heterogeneity. In general, evolution next generation global trends components focuses on

Language: Английский

Citations

25
Pushing the frontiers in the fight against antimicrobial resistance: the potential of fecal and maggot therapies DOI Creative Commons
Bashar Haruna Gulumbe, Abdulrakib Abdulrahim

Future Science OA, Journal Year: 2023, Volume and Issue: 9(10)

Published: Aug. 29, 2023

The escalating crisis of antimicrobial resistance (AMR) warrants innovative therapeutic strategies. Fecal microbiota transplantation (FMT) and maggot debridement therapy (MDT) represent paradigm-shifting approaches, leveraging biological systems to mitigate AMR. FMT restores a healthy gut microbiome, providing biotherapeutic counter pathogenic bacteria, thereby reducing reliance on traditional antibiotics. Conversely, MDT, form bio-debridement, utilizes the secretions maggots cleanse wounds eliminate resistant bacteria. Despite promise these therapies hold, their broader clinical adoption faces multifaceted challenges including need for rigorous scientific substantiation, standardized protocols, deepened understanding mechanisms action, surmounting regulatory public acceptance barriers. However, potential integration with precision medicine could revolutionize disease management, particularly antibiotic-resistant infections.

Language: Английский

Citations

18
Bacteriophages, gut bacteria, and microbial pathways interplay in cardiometabolic health DOI Creative Commons
Daniel Kirk, Ricardo Costeira, Alessia Visconti

et al.

Cell Reports, Journal Year: 2024, Volume and Issue: 43(2), P. 113728 - 113728

Published: Jan. 31, 2024

Cardiometabolic diseases are leading causes of mortality in Western countries. Well-established risk factors include host genetics, lifestyle, diet, and the gut microbiome. Moreover, bacterial communities their activities can be altered by bacteriophages (also known simply as phages), bacteria-infecting viruses, making these biological entities key regulators human cardiometabolic health. The manipulation populations phages enables possibility using treatment through phage therapy fecal viral transplants. First, however, a deeper understanding role phageome is required. In this review, we first introduce component microbiome discuss transplants relation to diseases. We then summarize current state research propose how might indirectly influence health bacteria metabolites.

Language: Английский

Citations

8
Exploring the Virome: An Integral Part of Human Health and Disease DOI
Amir Gholamzad,

Niloofar Khakpour,

Seyed Mohammad Ali Hashemi

et al.

Pathology - Research and Practice, Journal Year: 2024, Volume and Issue: 260, P. 155466 - 155466

Published: July 14, 2024

Language: Английский

Citations

5
The Future of Microbiome Therapeutics DOI Creative Commons
Milena Pitashny, Inbar Kesten,

Dima Shlon

et al.

Drugs, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 23, 2025

The human microbiome exerts profound influence over various biological processes within the body. Unlike many host determinants, it represents a readily accessible target for manipulation to promote health benefits. However, existing commercial microbiome-directed products often exhibit low efficacy. Advancements in technology are paving way development of novel therapeutics, across wide range indications. In this narrative review, we provide an overview state-of-the-art technologies late-stage development, examining their advantages and limitations. By covering spectrum, from fecal-derived live biotherapeutics, phage therapy, synthetic biology, illuminate path toward future therapeutics.

Language: Английский

Citations

0
Key Insights into Gut Alterations in Metabolic Syndrome DOI Open Access
Adrian Boicean, Cristian Ichim,

Sabina-Maria Sasu

et al.

Journal of Clinical Medicine, Journal Year: 2025, Volume and Issue: 14(8), P. 2678 - 2678

Published: April 14, 2025

Over time, extensive research has underscored the pivotal role of gut microbiota in onset and progression various diseases, with a particular focus on fecal transplantation (FMT) as potential therapeutic approach. The practice transferring matter from healthy donor to patient provides valuable insights into how alterations can impact disease development rectifying dysbiosis may offer benefits. Re-establishing balanced symbiotic relationship gastrointestinal tract shown positive results managing both intestinal systemic conditions. Currently, one most pressing global health issues is metabolic syndrome—a cluster conditions that includes insulin resistance, lipid imbalances, central obesity hypertension. In this context, FMT emerged promising strategy for addressing key components syndrome, such improving sensitivity, body weight profiles. However, further well-structured studies are needed refine treatment protocols establish long-term safety efficacy intervention.

Language: Английский

Citations

0
Gut microbiome associated dysbiosis: Limited regimens and expanding horizons of phage therapy DOI Creative Commons
Biplab Singha, Bhupendra Singh Rawat,

Ramya Venkataraman

et al.

Aspects of Molecular Medicine, Journal Year: 2023, Volume and Issue: 2, P. 100029 - 100029

Published: Nov. 21, 2023

Human gut microbiota plays an important role in health, broadly influencing metabolism to the immune system and drug resistance pathogenic colonization. Since antibiotic is on rise, wide-spectrum antibiotics are known have deleterious effects microbial biodiversity targeted therapeutic interventions must be made. Bacteriophages viruses that commonly recognized a high level of specificity, targeting only intended bacterial species without disrupting overall community. Advancements genomics, bioinformatics, synthetic biology led us identification design phages, capable precisely specific pathogens. In this review article, we aim discuss both challenges opportunities integrating phage therapies into clinical practice, discussing limitations traditional therapy as it pertains manipulation microbiome.

Language: Английский

Citations

6
Foodborne Clostridioides Species: Pathogenicity, Virulence and Biocontrol Options DOI Creative Commons
Mary Garvey

Microorganisms, Journal Year: 2023, Volume and Issue: 11(10), P. 2483 - 2483

Published: Oct. 3, 2023

Clostridioides species possess many virulence factors and alarming levels of muti-drug resistance which make them a significant risk to public health safety causative agent livestock disease. result in serious systemic gastrointestinal diseases such as myonecrosis, colitis, food poisoning gastroenteritis. As foodborne pathogens, are associated with incidences morbidity mortality where the application broad-spectrum antibiotics predisposes patients virulent colonisation. part One Health approach, there is an urgent need eliminate use production safeguard animals, humans environment. Alternative options warranted control pathogens at all stages production. Antimicrobial peptides bacteriophages have demonstrated efficacy against may offer antimicrobial biocontrol options. The bacteriocin nisin, for example, has been implemented biopreservative Listeria, Staphylococcus Clostridia food. Bacteriophage preparations also gained recognition antibacterial action highly bacterial including pathogens. Studies mitigate formulation administration limitations antimicrobials strategies. This review outlines species, their factors, potential

Language: Английский

Citations

4