Issue 259
Our Phage Picks for April 2024!
Here's the second rendition of our new format: Phage Picks — where we share the papers we keep bookmarked... and keep coming back to.
Sponsor
Sponsor
Join us for the Viruses of Microbes 2024 conference in beautiful Cairns, Australia to hear all about the latest advances in the field and reconnect with friends & colleagues. We are currently building the full scientific program, but there is still time to submit late-breaking abstracts until the 19th of April.
Community digest1alert5updates7jobs2posts
Phage alert
Urgent need for Peptostreptococcus/Finegoldia phages for a patient in Canada
We are urgently seeking Peptostreptococcus/Finegoldia phages for a patient in Canada.
Ways to help at this stage:
- By sending your phages for testing on the patient's strains
- By receiving the patient's strain and testing your phages
- By helping spread the word about this request
- By providing us with names/email addresses of labs you think we should contact
Please email staff@phage.directory if you can help in any way, or if you would like further details/clarification.
Let’s make a difference, Phage Directory
Updates
The LuxO-OpaR quorum-sensing cascade differentially controls Vibriophage VP882 lysis-lysogeny decision making in liquid and on surfaces, according to a new preprint by Francis Santoriello and Bonnie Bassler at Princeton University.
Phages avoid autoimmunity from cognate immune systems as an intrinsic part of their life cycles, according to a new paper by Jakob Rostøl (Imperial College London) and colleagues.
Phage banks are fragmented, and it’s time to unify them, according to a new review led by Gregory Resch (University of Lausanne) and including authors from Felix d’Herelle Center and DSMZ, two major phage repositories.
Phage-based technologies in the African AgriFood sector have major potential, according to a new report by Innovate UK as part of AgriFood Africa Connect.
Want a quick visual on global prevalence of Pseudomonas resistance to fluroquinolones? Or E. coli resistance to colistins? ResistanceMap is a new interactive visualization tool for looking at AMR around the world, created by One Health Trust.
Jobs
Pieter-Jan Haas’ group at UMC Utrecht is seeking a postdoc to identify the most relevant defense and counter defense mechanisms in clinical strains and phages of the bacterial pathogen P. aeruginosa.
The Villa lab at UCSD is hiring two Research Technicians to help understand structural dynamics and macromolecular interactions (including phage-host interactions) at high resolution.
The Lennon lab at Indiana University seeks a Research Associate to work on projects related to microbiology, ecology, and evolution, including dormancy (sporulation), phage infection, and plant-microbe associations.
The Alcaine Research Group at Cornell is seeking a technician in food science to help study microbial and enzymatic constituents of dairy, including bacterial cell culture, phage propagation, chemical and physical analysis of dairy products, and more.
Kevin Perthe at LKC Medicine, NTU, Singapore is hiring a Research Fellow to lead studies evaluating the potency and pharmacokinetics of therapeutic phages in animal models of bacterial infections.
Tina Liu’s lab at Rutgers University, New Jersey is hiring a postdoc to study molecular mechanisms of antiphage immunity in bacteria and archaea, focusing on the role and mechanism of CRISPR-associated nucleotide signaling.
The RIVER lab at EPFL (Switzerland) is seeking an intern (MSc student ideally) to collect phages from stream biofilms and study hosts, defense mechanisms, counter-defense mechanisms, and abilities phage can add to their hosts (lysogenic conversion), etc.
Community board
WHO Europe in collaboration with the Global AMR R&D Hub is hosting a webinar called ‘Towards building the evidence for broader use of bacteriophages from an AMR One Health perspective’ on April 18. This 1st webinar in a series of 3 will focus on opportunities and challenges facing application of phages for human health.
IDWeek 2024 (Oct 16-19, Los Angeles) is now accepting applications for their Pipeline Sessions and BugHub Stages, inviting companies and researchers to submit novel antimicrobial agents or diagnostic technologies for a chance to present at the conference. Applications are due June 26.
Hi everyone!
It's Phage Picks time! This is a new monthly format we're testing out. These are casual recommendations of papers — from colleague to colleague.
We hope these papers excite you as much as they excite us!
Phage Genome Annotation: Where to Begin and End
What is it about?
In this paper, Anastasiya Shen and Andy Millard provide us a much-needed and thorough guide to phage genome assembly and annotation. The paper covers anything from raw sequencing reads to submission of phage genomes through ENA. They include really helpful examples and scripts, databases, and software for all stages of the bioinformatics pipeline, as well as a decision-tree for phage genome reordering.
Why we’re excited about it:
Honestly, I’ve always been very confused whenever “bioinformatics” and “pipelines” were mentioned in the same sentence. I’ve always been confused as to why you couldn’t just “run a script and be done with it,” why it couldn’t be automated, and why sometimes “doing bioinformatics” on a phage or host could be so fast, and other times so slow. This paper shows how complicated phage bioinformatics can be, and how many decisions have to be made by the bioinformatician along the way to paint a “correct picture” of the phage, using its genome sequence.
~ Jan
Access: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9041514/pdf/phage.2021.0015.pdf
Shen A, Millard A. Phage Genome Annotation: Where to Begin and End. Phage (New Rochelle). 2021 Dec 1;2(4):183-193.
In Vitro Evolution to Increase the Titers of Difficult Bacteriophages: RAMP-UP Protocol
What is it about?
Danielle Kok and a few others from Heather Hendrickson’s lab down in NZ shows us two methods for experimentally evolving phages to increase their titers. The first method uses a traditional agar-overlay method over 25 days, whereas the other was a 96-well liquid infection protocol called RAMP-UP (Rapid Adaptive Mutation of Phage - UP) over 4-30 days — where phages are serially passaged with a modified Appelmans protocol. They also defined a math model to describe the limits of the approach.
Why we’re excited about it:
I’m not too good in the lab, but it doesn’t take a lab genius to figure out this could really benefit phage therapy. This protocol could possibly also help good phages get even higher titer yields. I’m also curious what happens when you make this higher throughput with liquid handling robots. Maybe the method could even unlock novel phages? But also… I’m curious if this changes the fundamental characteristics of the phage. Would this make the phage worse at therapy? No idea.
~ Jan
Access: https://www.liebertpub.com/doi/pdf/10.1089/phage.2023.0005
Danielle N. Kok, Joanne Turnbull, Nobuto Takeuchi, Philippos K. Tsourkas, and Heather L. Hendrickson. In Vitro Evolution to Increase the Titers of Difficult Bacteriophages: RAMP-UP Protocol. PHAGE. Jun 2023. 68-81.
The contribution of neutrophils to bacteriophage clearance and pharmacokinetics in vivo
What is it about?
Arne Echterhof and others from the Bollyky lab at Stanford and Felix Biotech wanted to know if neutrophils are one of the reasons phages don’t last forever in the body. This fits into a field called pharmacokinetics, which tracks the ‘impact of the body on a drug’. All drugs have to go through this, and yet phages generally haven’t. First, the team injected mice with phages; then they used qPCR and plaque assays to count phages in the blood and the spleen over time. They used two groups of mice; healthy and ‘neutropenic’ (given a drug to reduce its neutrophils). In both, phages dropped in the blood, but accumulated happily in the spleen; neutrophils didn't matter! They did see plaque assays lagging qPCR counts in blood though, suggesting there IS something inactivating phages… it’s just not neutrophils.
Why I’m excited about it:
This is a nice, straightforward example of phage pharmacokinetics! You put phages in the body, and you track where they go and how long it takes before they’re gone. This is a crucial part of drug development and one that the phage field hasn’t contended with too much (we just seem to skip animals and go straight to compassionate use in humans). (For years at phage therapy conferences I’ve heard grumpy pharma execs mumbling ”the PK/PD studies haven’t been done!”, and it was always on my to-do list to learn more.) With this study, we're one step closer to understanding what phages have to deal with (or don't) in the body! At least for the phage they tested (Pseudomonas phage LPS-5), neutrophils don't matter, but there's something in the blood that does.
~ Jess
Access: https://www.biorxiv.org/content/10.1101/2024.01.25.577154v1.full
Echterhof, A., Dharmaraj, T., McBride, R., Berry, J. D., Hopkins, M., Selvakumar, H., ... & Bollyky, P. (2024). The contribution of neutrophils to bacteriophage clearance and pharmacokinetics in vivo. bioRxiv, 2024-01.
That's it, those are our favorite drops for this week! We'll experiment with bringing you a new bunch of fresh picks every month — of a mix of 80's, 90's and today!
How were our picks this time? Suggest new papers, or tell us how to improve — just send them to me (Jan — jan@phage.directory)! Any feedback (nice or mean) will help us make Capsid more useful for you!
~ Jan & Jess
Jan Zheng, MHCI
I'm Jan, the other half of Phage Directory, and co-write Capsid & Tail.
Previously, I did data work at Phage Australia / Westmead Institute, where I built the biobank databases, data systems, and bioinformatics workflows for the clinical trial
I have a background in computer science and human-computer interaction, and I'm currently full-time at building the agentic layer for science at Nvidia.
Jessica Sacher, PhD
I'm a co-founder of Phage Directory and have a PhD in Microbiology from the University of Alberta (I studied Campylobacter phage biology). For Phage Directory, I help physicians find phages for their patients, and I'm always trying to find new ways to help the phage field grow (especially through connecting people and highlighting awesome stuff I see happening in the field).
I spent 2022-2024 as a postdoc in Jon Iredell's group at Westmead Institute for Medical Research in Sydney, Australia, helping get Phage Australia off the ground. I helped set up workflows for phage sourcing, biobanking, diagnostics, production, purification and QC of therapeutic phage batches, and helped build data collection systems to track everything we did. We treated more than a dozen patients in our first year, and I'm so proud of that!
As of 2024, I joined the Bollyky lab at Stanford University as a Staff Scientist, where I'm focused on phage engineering and delivery (to both microbial and human cells) and hydrogel-embedded phage cocktail development for wounds!