State of Phage #2: A wide diversity of strains

Issue 113 | February 12, 2021
19 min read
Capsid and Tail

We’re compiling the results of our State of Phage 2020 Survey, and we’re excited to show you a second snapshot of the findings! Today we’re focusing on strain collections; which bacterial species are phage labs collecting, how many do they have of each, and where did they get them from?

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We hope to see you there!!

What’s New

FDA has cleared Adaptive Phage Therapeutics to start formally investigating use of its PhageBank™ to treat prosthetic joint infections. This gives APT the green light to start a phase 1/2 clinical trial in the first half of 2021 in collaboration with Mayo Clinic.

Biotech newsClinical TrialPhage TherapyProsthetic joint infections

Sabrina Green (Baylor College of Medicine) and colleagues published a new paper in MBio showing that a novel phage uses its tail fiber to bind to certain mammalian gut glycans, which helps it better target its host in the gut by localizing it near the epithelial cell surface. This finding points to new strategies for using phages to target selected gut pathogens.

Gut phagePhages and glycansResearch paper

Ruby Lin (Westmead Institute for Medical Research) and colleagues published a new paper in Current Opinion in Biotechnology detailing their vision for a nationally-networked approach to personalized phage therapy in Australia, based around phage biobanking. Phage Directory is proud to be a collaborator on this work!

PerspectivePhage Therapy

Fatma Abdelrahman (Zewail City of Science and Technology, Egypt) and colleagues from 7 countries (Egypt, India, Nigeria, Australia, China, Pakistan, Spain), many of them early career researchers, published a new review in Antibiotics on phage lysins. We want to shine special light on this paper because it represents 12 authors from 7 countries who collaborated online during the pandemic to take this from start to finish. We’ve watched this group gather co-authors on Slack and What’s App, and work together to get this published. We think this paints a great picture of how global and how collaborative the phage community is, and hope to see more like this!

LysinsReview

Athina Zampara (University of Copenhagen, Denmark) and colleagues published a new paper in Frontiers in Microbiology on developing innolysins (endolysins fused to phage receptor binding proteins) against Campylobacter jejuni using a novel prophage receptor-binding protein.

LysinsResearch paper

Latest Jobs

Eligo Bioscience (Paris, France) is hiring a bioinformatics intern to help build, test and run a bioinformatics pipelines to help Eligo’s team engineer phages to target specific bacteria in the microbiome.
PhagoMed (Vienna, Austria) is looking for a (junior) researcher to join their team, which is developing synthetic phage lysins against chronic indications with high medical need.
The marine picophytoplankton ecology group at Linneaus University (Kalmar, Sweden) is hiring a postdoc fellow for a project investigating cyanophages infecting Synechococcus.

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!

The Africa Phage Forum is hosting its next phage webinar in its series, Feb 15 at 4pm GMT / 11am Eastern with special guest Dr. Evelien Adriaenssens, who will give a talk entitled Basics of phage genome annotation and classification - how to get started. Register now for this event and/or the whole series at https://apf.phage.directory.

Virtual Event

Analysis of phage genomes replete with hypothetical genes is a challenge. Given the importance of genomic characterization of phages to understand their biology and for their safe use, International Bacteriophage Research Consortium (IBRC) and Phage Directory are co-hosting a series of Phage Bioinformatics Webinars. This will be a beginner-focused series aimed at helping phage researchers get up to speed on phage genome characterization, including current practices, tools and tips, and will be taught by invited guest speakers.

The first webinar will be by Dr. Deborah Jacobs-Sera from the Hatfull Lab (University of Pittsburgh, USA), developer and overseer of phage discovery and genomics platforms for advancing science education, such as PHIRE and SEA-PHAGES. She’ll give a talk on “Genomic Annotation and Comparative Bioinformatic Analysis of Actinobacteriophages”, and will include an overview of tools such as DNA Master, GeneMark, Glimmer, tRNA Scan SE, Aragorn, HHPred.

We’re pleased to invite you to this series, beginning on 16 February, 2021 at 6.30 pm IST/8 am EST. Register for the first event here.

As a companion to this series, we’ve just launched a Slack channel called #phage-bioinformatics within the Phage Directory Slack (join here!), where you can share your questions and work through issues together with the community.

BioinformaticsVirtual Event

The sixth iVoM event will be Thursday, February 18, 11AM GMT (note time change!), and the theme will be “Biotechnology applications in health care”. It will feature talks by:
Laurent Debarbieux: Phages (in)action in the gut
Krystyna Dabrowska: A study that went wrong: phage engineering and phage pharmacokinetics
Tristan Ferry: Phage therapy experience in France in the field of Bone and Joint infection

Chairs:
Jeremy Barr
Joana Azeredo

Register at https://ivom.phage.directory.

Virtual EventViruses of microbesiVoM

Dear iVoM participants,
If you’ve attended at least two iVoM events, you’re invited to participate in a contest! The contest aims at having the audience feedback regarding the iVoM: Viruses of Microbes 2020 Webinar Series: Take a walk on the VoM side and expectations for the next Viruses of Microbes - the latest conquests on viruses of microbes conference. This must be done in a concise, clear, creative and attractive way, through the presentation of an image.

The winner will have the image published in the abstract book and a free registration for the next Viruses of Microbes Conference. See https://ivom.phage.directory for details.

Deadline for submission is Feb 16, so get your submissions in quickly! Winner will be announced at the last iVoM on Feb 18.

ConferenceContestVirtual Event

Phage enthusiasts need to take a 3-min break and watch this awesome student-made video breaking down phage lysogeny and the ‘Piggyback the winner’ hypothesis, set to the tune of a Justin Timberlake song… (no sound until around 0:26; then the music starts). Source: Ben Temperton’s BIO3099 class (University of Exeter).

Video

Listen to soil phage ecologist Gary Trubl talk soil microbes and viral ecology on the Storytellers of STEMM podcast!

Phage ecologyPodcastSoil viruses

Viruses has an upcoming Special Issue on ‘State-of-the-Art Phage Therapy Development in Europe’. They are looking for research articles, review articles and short communications related to: experimental and applied phage therapy; host–pathogen interactions and co-evolution; phage therapy in animal models; principle for selection and construction of bacteriophages for therapy; immune response to phage therapy; case studies; clinical trials. The deadline is the 31st of July 2021.

Special Issue

State of Phage #2: A wide diversity of strains

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Product designer and co-founder of Phage Directory
Co-founder
Phage Directory, Atlanta, GA, United States
Twitter @yawnxyz
Skills

Bioinformatics, Data Science, UX Design, Full-stack Engineering

Jan Zheng is a co-founder of Phage Directory and has a Master of Human-Computer Interaction degree from Carnegie Mellon University, and a computer science and psychology background from UMBC.

For Phage Directory, he takes care of the product design, engineering, and business / operations aspects.

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Phage microbiologist and co-founder of Phage Directory
Co-founder
Phage Directory, Atlanta, GA, United States

Jessica Sacher is a co-founder of Phage Directory and has a Ph.D in Microbiology and Biotechnology from the University of Alberta.

For Phage Directory, she takes care of the science, writing, communications, and business aspects.

We’re excited to share part two of the results of our State of Phage 2020 Survey! For this snapshot, we’re focusing on bacterial strain collections: which bacterial strains are phage labs collecting, how many do they have of each, and where do they get them from?

Read State of Phage #1: A wide diversity of backgrounds & phage experience here

A refresher: why we did this survey

The phage field is clearly growing around the world, but we realized that no one has collected a bird’s eye view of what everyone is working on. From our conversations with researchers, we believe that phage research activity and diversity of approaches is greater than the published literature would suggest. We created the State of Phage 2020 survey to fill this gap.

We hope it will help researchers learn more about how their phage research approaches compare with others around the world, and that it will help establish a baseline for the current state of phage research so we can collectively track how it grows and evolves over time. Check out part one of the survey results, which we wrote about here if you missed it, or want a refresher. In part 1 we focused on demographics, ie. who responded to the survey? What stage of career are they at, where are they located, and what level of phage experience do they have?

In future issues, we’ll release more data, digging into the phages people are collecting, where they got them, the kind of phage work they do, the methods they use, where they like to publish, their thoughts on sharing and commercializing phages, and more!

Our plans & hopes

This issue marks part two of a series that will wade through the data, looking at a different theme or two each time, but we’ll also publish a full report at the end of it all. We hope researchers will read it, learn lots about the field, and share it with others to inspire them to join the community and pursue their own phage research (or maybe fund it!).

Some caveats before we begin

Our survey is self-reported and importantly only approximates the phage field, so please take all insights we present with a grain of salt! The data is not statistically significant, and is highly biased towards Phage Directory’s reach. With that said, we can still glean lots of insights based on what we’ve collected!

Recap: who’s responded to the survey to date?

We’re thrilled to have received 136 full responses to our survey. Filling this thing out was no small feat, so thank you all so much for taking the time to let us know about the kind of phage work you’re doing!

Now, let’s dive in!

Why ask about strains?

All phages need hosts, so all phage labs must have bacterial strains. But how diverse and how large are these collections, and where did labs get them from? We wanted to ask about strains because even though labs may not report having phages targeting a certain strain, it’s probably only a matter of time until they start finding phages against it, if they’ve got it in their lab. Put differently, if anyone’s going to have a certain type of phage, it’s probably a phage lab who already works with that type of bacteria.

In total, respondents have collected bacterial strains spanning 62 genera and 133 species

First thing’s first: we found that 94.8% (129 labs) of our survey respondents reported that they have bacterial strain collections. We were excited to see that phage labs collect a wide diversity of bacterial strains! We weren’t sure what to expect going in (for instance, do phage labs tend to work on a small number of reference strains, or are they each specializing in their own bugs?). But as you can see from the word cloud below, there’s a pretty massive diversity of strains being collected.

The data shows that traditionally-considered reference species like E. coli and Staphylococcus are most popular, which is to be expected. We see the ESKAPE pathogens jumping out as popular strains to collect too, suggesting that clinically-relevant species are commonly collected. We also see lots of plant and animal-related strains. But from there, it’s a jungle!

Strain Word Cloud
Word cloud showing the 133 bacterial species collected by phage labs who responded to our State of Phage 2020 survey. Font size is proportional to number of labs who reported that species. View larger image

Collecting a few strains per genus is most common, but some labs have large collections of strains almost no one else has

For each bacterial genus collected, we asked respondents to estimate how many strains of that genus they had (either 1-10 strains, 11-50 strains, or 50+ strains). Most labs seem to collect fewer than 10 strains of a given genus (green bars in the graph below), but a fairly large subset of labs collect more than 10 strains of a given genus (yellow bars: 11-50 strains; blue bars: 50+). Interestingly, there are a few labs that collect very large numbers of strains for a some relatively unpopular genera, including Gardnerella, Dickeya, Pectobacterium, Yersinia, Vibrio, and Flavobacterium. We also noted that Mycobacterium, although widely known from the SEA-PHAGES program to be the genus used most commonly for phage hunting, is collected by only a minority of the respondents of this survey. This shows that most of our respondents likely do not come from the SEA-PHAGES program.

Strains Per Genus
Size of strain collections for each bacterial genus collected. View larger image

Each continent collects bacterial genera in its own proportions

We wanted to know where in the world different strains were being collected, to see if we’d see any interesting trends. We divided countries into continents/regions, then looked at relative proportions of bacterial genera collected by each. Some of the things we noted were that Klebsiella is as common as Escherichia in Asia, Salmonella is very popular in Africa, Vibrio is especially popular in South America, and Staphylococcus is less commonly collected than Escherichia and Pseudomonas across every geographic area. As expected, ESKAPE strains are popular around the world. We also noted that respondents from Europe report collecting the widest diversity of genera.

Asia Strains

South Asia Strains

North America Strains

European Strains

Oceania Strains

South America Strains

Africa Strains

Middle East Strains

Most labs collect 2-10 different species, with a quarter of labs collecting just one, and a few collecting >10

Looking more closely at the species composition of labs’ strain collections, a quarter of them (~34 labs) only collect one species in their labs. Half of respondents (~70 labs) collect between two and ten species. 15 labs (around 12%) collect more than ten species. 5 labs collect more than 20 species!

Labs vs. Num of Species
Number of bacterial species that labs collect.

Strain collections come in all sizes, and a third of labs collect at least 200 strains

We asked about the total number of strains, across all species/genera, that each lab collects. All sizes of collections were represented, with similar numbers of respondents reporting collections of under 50 strains as those reporting collections of 50 or more. Surprisingly, 42 labs (1/3) reported they have more than 200 strains in their collections!

Labs vs. Strain Collection Size

Total number of strains (across all species/genera) that labs collect.

Labs commonly isolate strains themselves or get them from collaborators; few strains came from culture collections

First, most respondents had kept track of how they acquired their strains — few selected ‘unknown’ as a source (we aren’t sure why, but we were assuming we’d see more!). We were surprised that most strains in labs’ collections seem to have been isolated by the lab itself or received from collaborators, rather from culture collections.

Strain Sources

How labs acquired their strains. View larger image

Labs have a good mix of environmental and clinical strains

In terms of original sources of strains, most respondents knew where their strains came from — again, few selected ‘unknown’ as a source. Most strain samples seem to have originated from the environment (though we didn’t ask for more specifics regarding type of environment; now we’re sorry we didn’t!). We were surprised at how many strains came from clinical sources (82 labs reported clinical strains, or 60%), indicating many of our respondents may be working on medically-relevant phage research. Relatively few labs seem to be getting strains from animal sources. Many write-in responses for sources of strains included variations of sewage/waste/feces or water/river/sea/aquatic. A few answers included “plants”. A few unique write-in answers include “Antarctic soil samples”, “insects from windowsill”, “created in our lab”, and “milk of buffalo suffering from mastitis”.

Strain Sample Sources
Original sources of strains (across all species/genera) that labs collect. View larger image

A closer look at ESKAPE strain collections

Given the popularity of ESKAPE and clinical strains, we took a closer look at this aspect of the data. We saw that 69 (50.7%) of survey respondents reported having ESKAPE strains*. All ESKAPE pathogens were represented by all collection sizes, suggesting there are large, medium and small collectors of all these pathogens. Acinetobacter, Enterobacter, and Enterococcus were underrepresented in strain collections compared to the more popular Klebsiella, Pseudomonas, and Staphylococcus. It will be interesting to see whether this correlates with the number of Acinetobacter, Enterobacter and Enterococcus phages we see (coming soon in part 3 of our survey results!).

*Note on ESKAPE strains: Tallying up ESKAPE strains accurately was a bit challenging, since the “ESKAPE” terminology combines species like “Klebsiella pneumoniae” and genera “Enterobacter spp”. A limitation of the survey is that we didn’t enforce reporting at the species level, so someone who reported “Klebsiella spp.” may have been using shorthand to refer to Klebsiella pneumoniae, or they may have been reporting a different Klebsiella species that is not considered an ESKAPE strain. Because of this limitation, we decide to look at ESKAPE genera only, meaning that we are including some non-ESKAPE species within these genera as well.

Strain Eskape Collection Sizes
Number of labs with different sizes of ESKAPE strain collections. View larger image

Conclusions

All in all, we saw that labs are collecting a wide array of bacterial species; that each continent has its own fingerprint when it comes to commonly collected strains; that most labs know the sources of their strains, and that they usually isolate strains themselves or get them from collaborators rather than culture collections; that labs have healthy mixes of environmental and clinical strains; and that ESKAPE strains are commonly isolated, with collections of each being gathered on small, medium and large scales.

How we generated the data

Jan used Observable to crunch the numbers, and used Google Sheets and Vega-Lite to generate the graphs.

Your feedback is welcome!

What are you surprised by from this issue? Did we miss anything? We’d love to hear your thoughts! Email [email protected] anytime!

Looking ahead to part 3

In the next State of Phage Snapshot issue, we’ll delve into phage collections. Given the wide range of strains collected, we’re really curious about how big the phage collections are that correspond to the strain collections reported.


Thanks to Sheetal Patpatia for her work writing summaries for the What’s New section this week!

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