Feeding phages to chickens: one of the first farm trials

Issue 43 | September 5, 2019
12 min read
Capsid and Tail

Cover Photo by William Moreland on Unsplash

How close are we to being able to treat chickens with phages? This week, we cover a recent study published by Viviana Clavijo and colleagues from the Universidad de los Andes in Colombia. They tested a 6-phage cocktail on chickens in a commercial farm setting and showed control of Salmonella incidence without affecting chicken productivity metrics.

Also in this issue: NIH puts millions into phage therapy research (which means new postdoc opportunities!), phages for food safety, new insights re: how cholera phage CTX enters its host, and more!

What’s New

An interdisciplinary research team at Georgia Tech and the Institut Pasteur has received a 5-year, $2.5 million NIH grant to study phage-immune interactions during treatment of respiratory infections with phages. The team is led by Joshua Weitz at Georgia Tech (computational modeling of phage-host-immune dynamics) and Laurent Debarbieux of the Institut Pasteur (phage therapy animal studies). If you want to work on this project, scroll down to see two new postdoc positions you can apply for!

Phage TherapyGrant FundingResearch

We’ve known for a while that Vibrio cholerae makes cholera toxin because of a phage, and that the phage’s receptor is Vibrio’s toxin coregulated pilus (Tcp). But how does the phage actually get in? Here’s a new paper by Miguel Gutierrez-Rodarte and colleages from Simon Fraser University in Canada that provides evidence that the tip of the CTX phage interacts with the tip of the pilus, followed by the phage being brought in as the pilus retracts!

ResearchPhage-host interactionsVibrio cholerae

The Oxford Bacteriophage Conference is happening next week (Sept 11-12 in Oxford, UK)! The scope: applying phage in medicine, food and biotechnology.

Are you going to this conference? We’re looking for a PhD student or postdoc to write a brief (500-700 word) recap for publication in Capsid & Tail. Email capsid@phage.directory if you’re interested!

ConferencePhage Applications

Interested in phages and food safety? Attend an open seminar in Aarhus, Denmark on Sept. 25. Learn about current foodborne disease trends in the EU, opportunities for producing safer fresh foods, and join discussions about the EU legislation for use of phages in fresh foods.

SeminarFood SafetyPhages in food

Need phage help? BB Phage Consultancy has just opened its doors! BB Phage is led by Ben Burrowes, PhD, and is based in Georgetown, Texas. They provide wet-lab services like phage isolation, purification and characterization, lab setup, protocol design and review, hands-on and classroom training, and more.

ConsultancyPhage services

Latest Jobs

Postdoctoral Research Associate in BREX and Phage-resistance mechanisms

Durham University, The Blower Lab

Dr. Tim Blower, Durham, UK

Applications are invited for a Postdoctoral Research Associate in BREX phage-resistance systems.

BREX methylates the host at specific recognition sequences, but the mechanism of BREX phage protection is not yet understood. This research programme contains three interconnected objectives: (1) Define the essential components and interactions within BREX loci using an E. coli model; (2) Define the biochemical activity and structure of BREX components and/or complexes; (3) Define how bacteriophages become BREX-resistant. These aims will be achieved using a range of techniques including microbiology, molecular biology, biochemistry, structural biology (X-ray crystallography, cryo-EM) and genomics. The project will be supported by two PhD studentships. The post is full time and fixed term for 36 months.

Tim Blower can be contacted for informal enquiries at timothy.blower@durham.ac.uk

Post Doc Molecular BiologyStructural BiologyBiochemistryPhage resistance

Postdoctoral Position: Phage Therapy

Institut Pasteur

Dr. Laurent Debarbieux, Paris, France

We are seeking a postdoc to join an NIH supported project on phage therapy to investigate the role of the immune system during the treatment of pneumonia initiated by the opportunistic pathogen Pseudomonas aeruginosa. This project will be carried out in collaboration with the team of Prof. Joshua Weitz (Georgia Tech, USA) – a group specializing in theory and models of viral dynamics. We are looking for a motivated candidate with a degree-qualified (MD, PhD, DVD) in microbiology, immunology, molecular biology, infectious disease, or closely related fields.

Post Doc Phage TherapyPhage-Immune Interactions

Postdoctoral Position: Virus-Microbe Dynamics

Georgia Institute of Technology

Dr. Joshua Weitz, Atlanta, Georgia

The postdoc will lead efforts to develop analytical and computational models of virus-microbe interactions with an emphasis on viral control of microbial community dynamics. Requirements include: (1) PhD in quantitative biosciences, physics, ecology, evolutionary biology, applied mathematics, or related area; (2) Strong quantitative & computational skills; (3) Excellent communication skills; (4) Interest and experience in collaborative research and model-data integration, including collaborative opportunities in the USA and France. Position to start in Fall 2019/Spring 2020; start date negotiable, includes competitive salary, benefits, and travel budget.

Post Doc Microbial community dynamicsComputational biologyVirus-host dynamics

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 30, 2019

Seeking collaborators for in vivo lung infection studies

Dr. Swapnil Ganesh Sanmukh

I am Dr. Swapnil Ganesh Sanmukh, presently working on my postdoctoral project (funded my MSCA-COFUND) entitled “Isolation of bacteriophages and lytic enzymes for targeted treatment of chronic bacterial lung infections”. I am looking forward to have collaborations for in-vivo studies. Please email me at swamukh1985in@rediffmail.com

In vivo studiesResearch

Feeding phages to chickens: one of the first farm trials

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Co-founder
Phage microbiologist and co-founder of Phage Directory
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’ve heard a lot recently about how important phage biocontrol could be to agriculture, and every phage conference seems to have at least a talk or two on using phages in agriculture. This week, we’re delving into a study published earlier this year, where a Salmonella phage cocktail was used in a farm setting to test its ability to control Salmonella in chickens.

The main source for this issue is: Clavijo, V. et al.(2019)

How bad is Salmonella?

Salmonella kills over 150,000 people a year, and infects over 90 million. Also, antibiotic resistance is a big problem with Salmonella.

How is Salmonella controlled in farms, currently?

Currently, it’s done in a multifactorial way, via antibiotics, vaccines, probiotics, prebiotics, and more.

However, as it’s becoming increasingly important that antibiotic use in agriculture is reduced, there’s an increasing need to find alternatives. Otherwise, we’ll see a rise in foodborne illness, and farmers will see big losses in productivity at the same time.

Have phages been tested in chickens before?

Yes, this has been done for decades, and has been reviewed extensively. However, most of these studies have been done using phages to target chickens in experimental settings, and not out in the field/on farms.

What’s hard about treating chickens with phages?

  • Phage specificity is a problem (need broad host-range cocktails)
  • A high enough phage inoculum can be hard to achieve (phages are usually given to chickens orally through drinking water, so high phage titres are needed)
  • Density of bacteria needs to be high enough to support phage replication (but waiting too long for bacterial densities to get high enough can mean there’s no time to treat with phages before chickens are slaughtered)
  • Studies in farms tend to lead to cross-contamination of phages between control and experimental groups, making data analysis a challenge

What’s nice about treating chickens with phages?

  • Cost-effective
  • Considered to be safe
  • Phage dosing can easily be carried out by farmers

The study

Clavijo, V., Baquero, D., Hernandez, S., Farfan, J. C., Arias, J., Arévalo, A., Donado-Godoy, P., & Vives-Flores, M. (2019). Phage cocktail SalmoFREE® reduces Salmonella on a commercial broiler farm. Poultry Science. DOI: 10.3382/ps/pez251

What they did and what they found

They used a 6-phage cocktail to treat Salmonella-colonized chicken flocks on a commercial Colombian chicken farm. They did two trials with about 30,000 chickens involved in each. They dosed the phages via drinking water (and had control groups for each), and they compared Salmonella incidence across groups. They found that the phages reduced Salmonella incidence, and that the treatment was safe.

Tell us about the phage cocktail used

The cocktail used was a 6-phage cocktail called SalmoFREE, produced and recently patented by the authors, and set to be commercialized by SciPhage, a spin-off company which works toward the development of phage therapy in Colombia (Viviana and Martha, two of the authors of this study, are part of the company).

Prior to this study, data about the cocktail’s phages (including genome sequence, host range, in vitro efficiency, and stability in chlorinated water) had already been documented.

A safety trial had already been carried out using chickens reared in battery cages (controlled conditions; not on a farm), where SalmoFREE® was given to chickens via drinking water. (The cocktail was found to be safe, as they saw no differences in mortality, weight gain, or feed intake.)

How was the dosing done?

They administered 3 doses of phages through drinking water (10^8 PFU/mL for 2.5 h; each chicken got around 30-60 mL per dose on average, dosing done on day 18, 27 and 35).

What kind of ethics approval did they need?

This study was approved by the Institutional Committee on Care and Use of Experimental Animals (CICUAL) from the Universidad de los Andes.

Why was this study different?

It took place on an actual farm, making it one of the first studies of its kind using phages. The only other one they point to was done with Campylobacter phages in Germany by Sophie Kittler and colleagues.

Did anything go wrong?

They ran into a few challenges. First, antibiotics were given to the chickens in their experimental group in the first of their two studies, since the veterinarian caring for them was concerned about increased mortality in one of the two experimental group houses (prior to phage treatment). So it was impossible to attribute Salmonella reduction in those chickens to the phages alone (although 3 days after antibiotics were given, they still detected lots of Salmonella, suggesting that those antibiotics were not effective against the organism).

Another challenge was that samples were spilled on the final day of the second study, so they didn’t get numbers from the final data point.

Another challenge was that they detected phages in the control chicken houses, suggesting cross-contamination of the phages (perhaps due to rubber boots of workers). (This was apparently also seen in the Kittler study).

They also detected phages in the control and experimental chicken houses at the beginning of trial #2 (done at the same farm as trial #1), meaning it was difficult to draw conclusions from the second trial.

Did the phages work?

Their cocktail appeared to reduce Salmonella incidence by up to 100%, though because of the issues described above, the phage treatment could only be partially attributed to the reduction.

Was it safe?

The phages didn’t appear to affect production parameters like chicken weight gain, feed conversion, weight homogeneity, or mortality rate, meaning it could be considered “innocuous”. In other words, the chickens seemed fine.

What does this all mean?

The safety and efficacy the authors observed is good news for their cocktail. Additionally, this study will help inform design of future trials for testing phage cocktails in poultry in the field, which have thus far been scarce. Lastly, the authors note that doing this study built trust with commercial poultry farmers, which is not to be understated, since adoption by farmers will likely be key to the success of any phage product.

It remains to be seen whether the levels of reduction these authors observed will lead to reduced food poisoning among consumers, though a reduction of even 50% at the pre-harvest stage has been predicted to prevent introduction of Salmonella into the food chain.

Main source for this issue

Clavijo, V., Baquero, D., Hernandez, S., Farfan, J. C., Arias, J., Arévalo, A., Donado-Godoy, P., & Vives-Flores, M. (2019). Phage cocktail SalmoFREE® reduces Salmonella on a commercial broiler farm. Poultry Science. DOI: 10.3382/ps/pez251

Other sources & further reading

Cover Photo by William Moreland on Unsplash

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