Issue 39 | August 1, 2019
12 min read

NCTC re-launches its phage collection

NCTC, a culture collection that supplies bacterial strains around the world, is re-launching its phage collection. How did this come about, and what does this mean for the phage community? We interviewed a group of NCTC microbiologists to find out.

Also in this issue: inoviruses everywhere, phages so concentrated they form a solid, phage-assisted evolution to make better gene editors, steps toward phages for food safety in Denmark, a place for phage therapy patients to tell their stories, how to get phage DNA from a low titer lysate, and more!

What’s New

Have an idea for us? Send us a tip!

Simon Roux and a multidisciplinary team of colleagues have found that inoviruses (filamentous, single stranded DNA phages that replicate without killing their host) are much more prevalent than previously thought, and they even infect archaea! Plus, this study gets into their biology, including how they interact with CRISPR. Paper | Behind the paper.

InovirusesMachine LearningArchaeal viruses

A research group at McMaster University led by Dr. Zeinab Hosseini-Doust has gotten phages to a high enough concentration to create a solid gel matrix. The phages self-assemble, and are still active against their bacterial host in this form. Paper | Press release

Materials engineeringPhage

Benjamin Thuronyi and colleagues from the Broad Institute and Harvard have developed a way to use phage-assisted continuous evolution to evolve better base editors for gene editing.

Gene editingPhage-assisted continuous evolution

The Danish project TOPSAFE (Targeted Optimized Phage solutions for food Safety), a 4-year collaboration between Danish businesses and researchers, is drawing to a close, and has shown that phages that target fresh food spoilage bacteria are ready to be scaled up for use in the food industry. A follow-up study focusing on reducing Campylobacter in poultry production, CAMPACT, will start soon.

Food SafetyPhage Biocontrol
Patient journalPhage Therapy

Postdoctoral position: Viral (phage) bioinformatics

Helmholtz Zentrum München Institute of Virology

As German Research Center for Environmental Health, Helmholtz Zentrum München pursues the goal of developing personalized medical approaches for the prevention and therapy of major common diseases such as diabetes mellitus, allergies and lung diseases. To achieve this, it investigates the interaction of genetics, environmental factors and lifestyle.

The institute of Virology is seeking a highly motivated postdoctoral bioinformatician for the newly funded ERC project, for omics analysis, with a particular emphasis on bacteriophage communities.

Post Doc BioinformaticsMetaviromicsPhage-host interactions

Research Technician: Phages against Pierce’s Disease

A&P Inphatec, LLC

A&P Inphatec, LLC is commercializing the first product to treat Pierce’s Disease in grapevines. Our unique solution utilizes bacteriophages to target and kill the bacteria at the source of the problem – giving wine growers an organic and sustainable solution to a rising threat in California.

A&P Inphatec, LLC is seeking a highly motivated and detail-oriented applicant to join our research and development team as a full-time Research Technician. This individual will be responsible for processing field trial samples, microbiological media preparation, and maintenance of cell stocks.

Research Technician Phages in agriculturePierce's DiseaseBiotech

Community Board

Anyone can post a message to the phage community — and it could be anything from collaboration requests, post-doc searches, sequencing help — just ask!

August 1, 2019

Community Q&A: Extracting phage DNA from low titer lysate?

This week on #phagetwitter: “Anyone have a good protocol for DNA extractions from low titer phage lysates?”@FazzinoLisa

Check out the thread for many helpful answers and links!

#BestOfPhageTwitter

NCTC re-launches its phage collection

NCTC stands for the National Collection of Type Cultures. It is best known as a bacterial culture collection run by Public Health England, but it also includes a phage collection. Recently, NCTC announced that it was re-launching and re-characterizing its phage collection. We asked four NCTC microbiologists about how this came about and what it means for the phage community.

Has NCTC always had a phage collection? Or how long ago did NCTC begin collecting phages?

There was certainly no phage collection when NCTC was established by the Lister Institute of Preventative Medicine and Medical Research Council in 1920. The collection was relocated to the Central Public Health Laboratory (CPHL) in Northwest London in 1949, becoming the responsibility of the nascent Public Health Laboratory Service (PHLS), a precursor organisation to Public Health England. This transfer heralded a change in remit for NCTC, with a new specific focus on bacteria of medical and veterinary importance.

The close association with PHLS enabled NCTC to serve as a Reference Laboratory collaborator, extending the range of strains available through NCTC to the wide variety of pathogens sent from hospital laboratories to CPHL for identification and specialist testing. At that time, phage typing was used by some of the Reference Laboratories to distinguish between bacterial strains of the same species, and was one of many techniques used by the PHLS to help study the epidemiology of infectious diseases.

The NCTC bacteriophage collection can be split broadly into three groups: the Staphylococcus phages were deposited by the PHLS Staphylococcal Reference Laboratory staff between 1950 and 1974, the Streptococcus phages deposited by Jacqueline Stringer in 1979 following the development of her phage typing scheme for group-B streptococci in 1979, and a set of Campylobacter phages deposited by D. Hutchinson in order to develop the Preston Public Health Laboratory (PHL) in 1992.

Can you tell us a bit about where NCTC’s phages have come from, and why those particular phages were archived?

Most of the phages held by NCTC were collected and made available to microbiologists for their value in bacterial typing (phage typing), as access to the same standardised sets of phages means that data can be compared between laboratories. So at the time of inception of the phage collection, they were only used because of their specificity for certain strains of bacteria and were used for typing these strains.

Now, however, there is a whole lot more that we can do with phages, and the more metadata we can obtain about each phage, the better for the scientific community. The specific features of these phages are yet to be fully uncovered, which is what we are delivering with this characterisation project.

Can you tell us about NCTC’s planned re-launch of its phage collection? What will be the differences between the new and the old system?

Previously, people have been able to buy phages from the collection without much information about them other than their propagating or host strains. With the re-launch of the collection, much more data will be available to the user, such as to which family the phage belongs, information about host range, and suggested incubation/propagation conditions and buffers to use. There is still plenty to be done in terms of fully characterising the collection, such as genomic analysis, but what we can now offer is so much more than was previously available. NCTC plans to re-launch its collection sometime in September/October this year.

What made NCTC recently decide to start re-characterizing its phages/focusing on promoting its phage repository?

We think it is fair to say that there has been a surge in interest in phages in recent years, as scientists look for alternatives to antibiotics in light of the crisis relating to antimicrobial resistance (AMR). We identified the potential importance of this collection, and are confident that making these phages more accessible to researchers and biotech companies worldwide who are seeking solutions to AMR is the right thing to do; the timing seems judicious.

Are NCTC phages able to be used for therapeutic and commercial purposes, or just for research?

NCTC phages have not been tested for efficacy as therapeutic agents, so we cannot comment on that aspect. This is not to say that they have no therapeutic potential, but what we hope to see is researchers accessing these phages and uncovering any such potential that has not previously been identified. We can confirm, however, that they are available for commercial purposes.

Can you tell us about NCTC’s phage depositing process?

Although we have thus far not accepted any new phage deposits while establishing our processes, there certainly are numerous enquiries about depositing phages into NCTC by scientists across the world. However, with the forthcoming re-launch of the phage collection, and with the phage community becoming aware of this resource, we expect that to increase further. Just like our bacterial collection, it is free to deposit phages, and the depositor can later, should the need arise, request a sample back at no cost.

How does NCTC handle material transfer agreements and intellectual property regarding deposited/requested phages?

Each material transfer agreement and IP is upon individual request. Since each case is unique, NCTC handles these requests on a case-by-case basis.

Does NCTC offer phage/host sequencing or characterization services?

NCTC does not yet offer a phage sequencing service, but it is envisaged that this could be a future direction for the phages. As mentioned earlier, we aim to collect as much metadata as possible about the phage and host strains within the collection, so watch this space!

What’s the biggest challenge NCTC faces with regards to its phage repository?

I suppose it is the scarcity of data about the specific phages. The flow of information over the years since deposition has meant some data has been lost, or is not as modern as we would like. Also, the staff who used to work on phage typing have now all moved on or retired from PHE. This challenge is exciting in the sense that you approach each phage as though it were completely new, and you have no information about it other than in relation to its propagating strain.

The advantage of this repository is that there is the availability of purified and well-preserved, freeze-dried phages in glass ampoules. You are not dealing with a variety of phages within the one sample, such as you might have with an environmental sample, but one that has already been isolated and purified. Once the genomic data is available for these strains, who knows what that might reveal? These could be well known phages already in use, or may be completely new ones. There is a lot to uncover and that is going to change as we make them accessible to the wider community.

What are the most popular phages ordered from NCTC?

The Staphylococcus phages are popular, but we have had demand across the range of phages in the collection over the years since 2005 when we started monitoring this.

Is there anything else you’d like to highlight?

NCTC would like to just use this opportunity to commend you at the Phage Directory for this great initiative to curate phage data worldwide and help with accessibility and information about phage banks and the services they provide. Our message to the wider phage, biotech and pharma communities out there is that NCTC’s dynamic collection is here to access, it will expand as we receive more phages, and we are very versatile and flexible in terms of the deposition process.

How can the phage community get in touch if they’d like to access/deposit phages, or if they have more questions?

We encourage people to get in touch with their questions and thoughts about phages and the specific collection. We hope to see an interest in our phages from which future collaborations with appropriate organisations and/or individuals looking to join (or who are already in) the fight against AMR can develop.

Direct any enquiries to culturecollections@businessenquiries.gov.uk.

Further reading

For more on phage banks, check out our past Capsid & Tail article on phage banks around the world.

For more on Phage Directory’s plans to curate phage data and to catalogue phages, check out the What’s New section of last week’s Capsid & Tail!

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