Quick Dive: Diabetic foot ulcers and phage therapy

Issue 116 | March 5, 2021
9 min read
Capsid and Tail

Photo by Julie Fung

Today we’re doing a quick dive into diabetic foot ulcers and phages. What’s the problem, what are some ways phages have been used to date, and what’s the current status of clinical trials?

Urgent March 5, 2021

Urgent need for Bacillus simplex phages for a patient

Phage Therapy

We are urgently seeking Bacillus simplex phages for a patient in the USA.

Ways to help at this stage:

  • By sending your phages for testing on the patient’s strain
  • By receiving the strain and testing your phages
  • By receiving the strain and using it to search for new phages against the organism
  • By helping spread the word about this request
  • By providing us with names/email addresses of labs you think we should contact

Please email [email protected] if you can help in any way, or if you would like further details/clarification.

Let’s make a difference,
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What’s New

BCM TAILΦR Labs (Tailored Antibacterials and Innovative Laboratories for phage (Φ) Research) and a team of their collaborators was awarded a 7.5 million dollar U19 grant by the National Institute of Allergy and Infectious Diseases. Congrats!!

Grant funding news

Martin Jahn and colleagues recently published an interesting paper on the lifestyle of phages of marine sponges by host prediction and correlative microscopy. They used a new correlative in situ imaging approach (‘PhageFISH-CLEM‘) to localise phages within bacterial symbiont cells, but also within phagocytotically active sponge cells. Martin also did a short Twitter thread about it.

Community contributionMarine phagesResearch paper

Luis Camarillo-Guerrero (Wellcome Sanger Insititute) and colleagues published a paper on the prevalence of viral diversity in the human gut, along with a new Gut Phage Database (142,809 non-redundant gut phage genomes from 28,060 metagenomes!). They confirmed distribution of huge viral clusters on different continents featuring p-crAssphage characteristics, corroborating the human lifestyle-associated global variation in the gut phageome.

Gut phageomeResearch paperViral metagenomicscrAssphage

Few have explored how phages affect bacteria associated with winemaking. Cécile Philippe (University of Bordeaux, France) and colleagues published a new paper in Frontiers in Microbiology on the characterization of the first virulent phages infecting Oenococcus oeni, the lactic acid bacterium considered ‘the Queen of the Cellars’. Analysis of their genomes shows these phages have mosaic genomes unique among lactic acid bacteria-infecting phages.

Lactic acid bacteriaResearch paperWinemaking

Varun Rakeshbhai Bavda (IISER, India) and colleagues published a new article on the molecular properties of mycobacteriophage D29 Holin, with an emphasis on potential for holin engineering. They demonstrated crucial amino acid regions for holin-mediated toxicity, as well as how amino acid substitution in the C-terminal region renders the holin non-toxic. They have also engineered a holin which shows higher toxicity in some strains.

HolinResearch paperbioengineering

Latest Jobs

PhD projectPost Doc
Two openings in Rafal Mostowy’s group in Krakow to work on bioinformatics of bacteria-phage interactions: 1. Postdoc to study phage proteome/domainome and 2. PhD to study role of HGT in phage evolution. See his Twitter thread here.
Director
Locus Biosciences, a phage biotech company in North Carolina, is hiring a director of translational medicine.

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!

Later this month, leading drug developers, academics and clinical researchers will come together at the 3rd Bacteriophage Therapy Summit to address their translation challenges, from characterization of phages through to clinical development. Join them online to strengthen your product development pipelines and forge new collaborations to unlock the full potential of bacteriophage therapeutics. Use code PD10 to get 10% off!

Virtual EventPhage TherapySponsor

PHAVES #13 will be a seminar with Prof. Jonathan Iredell, MBBS, PhD of the Westmead Institute for Medical Research and University of Sydney on Wed, March 10 at 8AM AEDT (Tues, March 9 at 4PM Eastern Time/10PM CET). He will give a talk entitled Phage Therapy: The Australian Experience. Small group networking to follow! Register here!

PHAVESVirtual EventPhage Therapy

The Texas Medical Center (TMC) Digestive Diseases Center 12th Frontiers in Digestive Diseases Symposium “Phages, Viruses, and Digestive Diseases” will take place Saturday, March 6, 2021, 8 am CST – 1:45 pm CST. Event Organizers: Mary K. Estes, Ph.D. and Anthony Maresso, Ph.D. Register here.

Gut phageVirtual Event

Thanks to all who attended 2021 Phage Futures Congress last week! The conference conducted a Young Researchers Poster Competition, and announced the four finalists on the last day.

Congratulations to:

  • Carmen Gu Liu (Baylor College of Medicine) “Lighting Viral Dark Matter: Revealing Earth’s Cryptic Genosphere Through Environmental Sampling”
  • Matti Ylanne (University of Helsinki) “Phage therapy treatment of chronic sinusitis caused by Pseudomonas aeruginosa”,
  • Meaghan Castledine (University of Exeter) “Parallel phage resistance – virulence trade-offs during clinical phage therapy and in vitro”
  • Stephanie Lynch (La Trobe University) “Phage therapy for Staphylococcus pseudintermedius infections in canines.”

Everyone, even those who didn’t attend the conference, is invited to attend the free webinar 10th March 2pm EST, where these four winners will present!

AwardEarly career researchersPhage TherapyVirtual Event

We are in search for Pseudomonas aeruginosa phage PaP3, it was described by Fuquan Hu’s lab but myself and Prof. Gino Cingolani haven’t received a reply from them. Hope you can help us find this prophage or a similar one to this and LUZ24 (we required a temperate phage). Thank you! Contact details: [email protected].

Seeking phages

Quick Dive: Diabetic foot ulcers and phage therapy

Profile Image
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 going to start doing more ‘quick dives’ into topics relevant to the phage community: this week, we’ve chosen diabetic foot ulcers.

We’ll also be setting up a roundtable to bring together those working in this space; see below for details, & email [email protected] if you’d like to take part!

Diabetic foot ulcers are extremely common, and often lead to amputation

Every 20 seconds, someone loses a limb to diabetes, and it often starts with a foot or toe ulcer (wound). Diabetic foot/toe ulcers are extremely common in diabetic patients, and around half get infected, but antibiotics don’t work well. These infections often lead to amputation of the toe, which often leads to amputation of the leg, which often leads to mortality within a few years.

Antibiotics often can’t get to the wound because of poor blood flow in these patients. There’s also the issue of biofilms, which also lead to antibiotic treatment failure. Staphylococcus aureus is a major pathogen associated with these infections, but many other species can be involved.

Diabetic foot ulcers are good candidates for phage therapy

Diabetic foot ulcer infections are considered a good indication for phage therapy — the wounds are accessible, antibiotics don’t work well, and it’s easy to watch progression/healing of the disease. Many consider this a “low hanging fruit” when it comes to picking a clinical indication to go after with phages.

To date, phages have been used to treat diabetic ulcer infections in human and animal studies. See Duplessis et al. (2020) for a recent comprehensive review.

Case reports suggest phages help close wounds and prevent amputation

Randy Fish, a podiatrist in Washington, USA is one of the clinicians who has used phage to treat DFU infections. He used a phage, Sb-1, from the Eliava Institute in Tbilisi, Georgia to treat several patients, and all his patients ended up with closed wounds instead of amputation.

Randomized clinical trials are underway

  • TechnoPhage in Portugal is starting a Phase I/IIa clinical study to test a phage candidate against diabetic foot infections. They’ll test safety and tolerability, as well as ability of phage to reduce target bacteria (P. aeruginosa, S. aureus, A. baumannii). Results are expected in 2021

  • PhagoPied is a clinical efficacy study starting soon, sponsored by Centre Hospitalier Universitaire de Nīmes, France in collaboration with Pherecydes Pharma. They’ll test efficacy of standard treatment + phage (targeting S. aureus) versus standard treatment + placebo in treating diabetic foot ulcers, looking at safety, tolerability, and wound healing in 60 patients

  • University Hospitals of Derby and Burton NHS Foundation Trust announced a clinical trial on ClinicalTrials.gov to test anti-Staphylococcus phages in diabetic foot ulcers, but funding issues have halted this study for the time being

Do you work on diabetic foot ulcers and phages, or want to meet others who do?

We want to identify more people working on phages to treat diabetic foot ulcers, and those dealing with this problem in the clinic. We’re looking at setting up a virtual roundtable to foster collaboration opportunities and see what gaps still need to be filled.

If you’re a clinician who treats diabetic foot ulcers, a biotech professional or researcher working on phages for this problem, a patient dealing with these infections, or if you’re just interested in further discussions in this space, please get in touch by emailing me at je[email protected].

Further reading

There’s much more to read on this subject; this quick dive was just meant to scratch the surface!

For a recent comprehensive review of topical phage therapy for chronically infected wounds, including but not limited to diabetic foot ulcers, see this one by Duplessis et al (2020).


Thanks to Atif Khan, Sheetal Patpatia and Leon Steiner for contributing summaries for the What’s New section this week!

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