Thread by @WvSchaik

Delighted to be @uniofleicester today for the launch of their Centre for Phage Research (no Twitter account yet, @milja001?)

Totally original opening of proceedings by a live rendition of 'Pulled In A New Direction' from the Addams Family

Now @MarthaClokie introduces the day, and the potential for the use of phages across different modalities. And the Centre for Phage Research has a Twitter account: @Leicester_Phage !

Martha highlights how every bacterium will have its own phages, the vast majority of these remain to be discovered. She is showing cool figures generated via phageclouds.dk

Aims of @Leicester_Phage are to establish a curated UK phage bank, build UK capacity for phage research, have clarity on regulatory pathways to direct data collection & purification practices, progress existing products to translation and teach next generation of phage biologists

Steven Webb (UKRI) highlights the five strategic themes of UKRI, with tackling infections (emerging pathogens, AMR) being one of them.

Steven highlights that landscape across human, animal and planet health to study infections could be more integrated across the UK.

SW: flagship networks on epidemic preparedness and AMR being set up.

SW: AMR flagship, aims to connect and expand UK AMR research communities + link to stakeholders. Particularly important to breakdown siloes between disciplines.

Visual representation of AMR networks

Next speaker is Francesca Hodges from @innovateuk, knowledge transfer manager in the emerging technologies and industries theme.

Highlights the large number of use cases for phages: food production/safety, livestock production, veterinary medicine, aquaculture, crop production, skin care, human medicine.

Innovate UK is supporting the Phage Innovation Network, launched 6 months ago iuk.ktn-uk.org/news/innovate-…

Next up: @milja001 on phage genomics: 20% of nucleotides on Earth are viral, <1% of nucleotides in NCBI are phage/viral -> viruses are very understudied, much new biology remains to be discovered.

Andy highlights recent developments in genomic taxonomy of phages pubmed.ncbi.nlm.nih.gov/33803862/. 75% of isolated phages on only 30 bacterial genera.

It is important to understand genomic diversity of phages as efficacy of phage combinations increases with phage diversity microbiologyresearch.org/content/journa…

Recent work should that phage tropism could be predicted from genomic data in Klebsiella phages cell.com/cell-reports/f…. Opportunity to link genotypic and phenotypic data across different species.

Important to screen for absence of phage-encoded virulence factors and antibiotic resistance genes (ARGs): phages carrying these are relatively rare

Phage-mediated Horizontal Gene Transfer: some phages have been identified to lead to 'super spreading' of resistance genes. Genomics will allow the identification of similar phages that may act similarly in other hosts. pubmed.ncbi.nlm.nih.gov/28096488/

Interesting case study to link phenotype (increased hear resistance, broader pH range) to genotypes in phage biology pubmed.ncbi.nlm.nih.gov/35056115/

Andy finishes by saying that we need more and better genomic data, and from a wide range of bacterial hosts

Next session is on phages and food safety/security. First speaker is Alison Blackwell of @APS_Biolyse (apsbiocontrol.com) who works to use phages to prevent bacterial diseases in agriculture and food production, thereby reducing food waste + improving food security.

Alison highlights the exciting opportunities around phages as biocontrol agents, but there are significant regulatory challenges around phage plant protection products.

Now a presentation of @GeoAldridge a 3rd year PhD student @Leicester_Phage on the use of phage to combat soft-rot disease.

Soft rot diseases is a bacterial disease of vegetables and ornamental plants. Losses of soft rot disease in the UK potato industry is £50 mln/year.

George aimed to isolate and characterise bacteriophages against soft-rot disease-causing bacteria, understand dynamics in phage cocktails and test for effectiveness in a potato model.

He collected samples from soil, potato wash water and irrigation water and performed plaque assays to screen for presence of phages active against soft-rot bacteria.

George has so far collected and sequenced 27 new bacteriophages. Diverse collection, 39 - 150 kbp genomes. Several broad host range phages, active against multiple species/strains of soft-rot bacteria were identified.

Great case study in the potential of phages as plant protection agents. Now a panel discussion, which will be difficult to live-tweet. I'll be back in about 45 mins.

(good #Eurovision Finland cha-cha-cha joke to round up the discussion)

Next up, session on phages in animals, with the first speaker Rajesh Odedra, R&D Director of @carus_ah.

Rajesh is highlighting the difficulties around the regulatory landscape for bacteriophage-based products [this is a real issue around the implementation of phages in agriculture/veterinary and clinical medicine].

First case study is on the use of phages in the treatment of pyoderma (caused by Staphylococcus pseudintermedius, increasingly multidrug-resistant) in dogs

In vitro screening found phage candidates that specifically targeted S. pseudintermedius strains associated with pyoderma.

Formulation for phages needed to be developed: challenging (e.g. long shelf-life needed). Using @FixedPhage technology to reach good stability and increased activity. Application of bacteriophage preparations has now begun.

Second application for phages: canine oral health, particularly a problem with dogs with squished faces (French bulldogs, I think). Plaque + further complications associated with keystone species Porphyromonas gulae -> develop phage-product against them.

In vitro canine dental plaque model showed that application of phage could reduce biofilm by 20%. Phages can be attached stably to dog treats.

Final case study: closed-loop facilities that retain and treat water in aquaculture farms. Working to minimise risk posed by Flavobacterium psychrophilum in salmon farming.

Relevant work on F. psychrophilum phages here liebertpub.com/doi/10.1089/ph…. Bacteriophages attack the type IX secretion system. Bacteria can evolve resistance by then they become non-pathogenic and fail to form biofilms.

Another example: livestock produces 44% of all anthropogenic methane (powerful greenhouse gas); vast majority of methane is produced by Archaea (Methanibrevibacter smithii).

Now identifying, characterising phages that attack Archaea; phage exposure leads to 80% reduction of methane production in vitro. Now developing formulations for in vivo trials.

now again highlighting regulatory challenges for phage formulations discussed in the presentation, major differences between EU, UK, USA; greatly complicates matters!

Now Anisha Thanki, a post-doc @Leicester_Phage on anti-Salmonella phages to ensure food safety.

Anisha has isolated phages against Salmonella and is now showing data using a Galleria mellonella larvae infection model, showing efficacy of phage cocktail.

Now on to poultry trials, tested for optimal route (in feed, in water). I missed whether Salmonella is given first, then the phage or vice versa.

Phages delivered in feed showed efficacy: lower number of pens that Salmonella could be isolated from compared to control, after challenge with Salmonella. Phages delivered in water are faster-acting, and more effective.

Very exciting results, one of the most convincing use-cases for phage therapy in agricultural settings I know of. I believe this study has not yet been published.

Final session focuses on the use of phages in human medicine. First speaker is Josh Jones, NHS Clinical Phage Specialist/Director UK Phage Therapy

Systematic review of phage therapy since 2000: 2241 clinical cases, 79% patients showed clinical improvement thelancet.com/journals/lanin…

USA regulators have concluded that there is sufficient evidence for phage therapy in cases of antibiotic-refractory infections.

Did not catch all relevant references here.

Josh highlights this paper on the future of phage therapy in the United Kingdom: mdpi.com/1999-4915/15/3…

Most future use of phages in the NHS will be through the use of phage cocktails, with additional use of 'personalised therapeutic phages'

Next speaker is @Akis_BeCool, on the use of phage therapy in complex lung settings.

Chronic lung disease a major cause of morbidity and mortality. The lung microbiome is complex and phage therapy is better suited for disease management rather than crisis management.

Evidence-based medicine of phage therapy in respiratory diseases will include: restoration of the resilience of the microbiome, include complex linkages in social-ecological systems and two other factors that I failed to catch.

great, conceptual overview of the use of phages in human medicine, and particularly in respiratory conditions (difficult to capture in tweets though!).

Now @MarthaClokie is wrapping up today's excellent meeting.

Some shared themes across the meeting: agreement on the efficacy of phages; challenges include finance, regulation, production; practical ways going forward: work with end-users (farmers, clinicians); opportunity for post-use surveillance of phage therapy

More opportunities for funding phage therapy research through UKRI and other routes [I noticed many public-private collaborations in this meeting].

Plans are being made for a similar
event next year. Thanks @Leicester_Phage for organising this excellent meeting!