Phages against porcine enterotoxigenic E. coli: a Christmas tale

Issue 57 | December 20, 2019
7 min read
Capsid and Tail

Visiting a farm with piglets just weaned. Photo credit: Michela Gambino.

This week, Dr. Michela Gambino, a postdoc in the PHAGEBio group at the University of Copenhagen, tells us about the importance of pork in Denmark, and about their group’s search for phages against E. coli in pigs.

Also in this issue: how phages impact desert biocrust bacteria, new antibiotic resistance and phage therapy research funding from NIAID, a milestone for a Colombian phage biotech startup, and more!

What’s New

NIAID will renew funding ($102.5 million over 7 years) for the Antibacterial Resistance Leadership Group (ARLG), and this time it includes funds for a phage therapy study! The ARLG is a global consortium of scientific experts that leads a clinical research network for antibacterial resistance studies.

Grant FundingPhage TherapyClinical Trials

Biocrusts are photosynthetic hotspots in deserts that face an uncertain future due to climate change-induced changes in rainfall. Marc Van Goethem (Lawrence Berkeley National Labs) and colleagues have published a study in mBio characterizing phage-host dynamics in response to biocrust wetting. Their results suggest that phages control populations of spore-forming bacteria in biocrusts, and that phages may influence and even benefit from host sporulation dynamics.

ResearchSoil phages

Sci Phage, a Colombian phage biotech company commercializing a Salmonella phage cocktail for use in chicken farms, is one of three winners of the Latin American startup accelerator program GaneshaLab. GaneshaLab will support winning companies as they begin entering the US market.

BiotechPhage Biocontrol

Here’s an excellent recent documentary about the history and state of phage therapy by ARTE, a French/German public broadcast service (54 min). It’s available until Dec 31 and well worth the watch!

For more, read last week’s Capsid & Tail, where Aël Hardy interviewed two of the physicians featured in the film.

Phage Therapy

The 2nd Hanson Wade Bacteriophage Therapy Summit will take place March 24-26, 2020 in Boston. Key speakers include representatives from the FDA and the EMA, as well as leaders of several phage biotech companies.

ConferencePhage TherapyBiotech

It’s almost the holiday season! Here’s Harvard postdoc Siân Owen’s template for making paper phages to decorate your lab or office! (Of course, these are worthwhile to make year-round!)

Phage Phun

Latest Jobs

Academic Faculty BioinformaticsChemical BiologyStructural BiologyPhage Biology

Associate Professor

University of Toronto is hiring for a phage-related faculty position: “We are interested in candidates who are applying bioinformatics, chemical biology and structural biology to important questions in the biology and biochemistry of bacteriophage life cycles.”
Academic PhD Project Phage EngineeringAntibiotic Resistance

PhD Studentship

Jessica Blair (Univ. of Birmingham) and Martha Clokie (Univ. of Leicester) are recruiting a PhD student to work on using phages to turn off bacterial efflux pumps.
Academic Faculty GenomicsGeneticsEcology

Two faculty positions

Monash University in Melbourne, Australia is hiring faculty in Genomics/Genetics and Ecology/Environmental Sciences.

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!

Happy holidays — See you in the new year!

Merry Christmas! We’ll be taking a break from Capsid & Tail next week, but we’ll be back in the new year, starting with a reflection on 2019 and a look at where Phage Directory is headed in 2020!

P.S. If you’re interested in contributing a Capsid & Tail guest article in 2020, check out our guidelines and register your interest here!

Phages against porcine enterotoxigenic E. coli: a Christmas tale

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PHAGEBio Group, University of Copenhagen, Copenhagen, Denmark

Michela Gambino is a postdoc in the PHAGEBio group, headed by professor Lone Brøndsted, at the Department of Veterinary and Animal Sciences, University of Copenhagen. During her PhD, she studied microbial communities and how stress affect their development at the University of Milano. Then, she switched to phages. She is interested in how microbial and viral communities interact and evolve in the environment, both in natural and artificial niches.

The importance of being a pig in Denmark

Copenhagen is beautiful during Christmas time. The lights, the smell of cinnamon and caramelized almond, the Christmas songs at the market. Danes are very proud of their Christmas traditions, and as an Italian expat in Denmark, my main interest has always been food. Flaskesteg is considered one of the principal national dishes: a joint of pork with a crunchy crust, served with baked potatoes and thick brown sauce…delicious!

Pork is not only a pillar of Christmas traditions, but its production permeates Danish culture deeply. Denmark is one of the most important countries for pork export and some say that in this tiny country there may be more pigs than people. For such a large production, investments are huge and the growing consensus for animal welfare pushes this industry to look for innovative and economically sustainable solutions.

SOS: alternatives to zinc oxide for the biocontrol of post-weaning diarrhea

One of the main issues hitting pork production in Denmark is post-weaning diarrhea. The disease results from many factors, but the main cause seems to be a special pathotype of Escherichia coli, called enterotoxigenic E. coli (ETEC). Once they enter the piglet’s gut, ETEC have specific appendages to bind to the gut cells and they release toxins that cause diarrhea. So far, the use of zinc oxide has limited the spread and infection of these ETEC, with a bearable economic loss for pig industry. Unfortunately, zinc oxide has been correlated with the transfer of antibiotic resistance genes and has a detrimental effect on the environment. For these reasons, it has been banned from Europe in pork production by 2022. The fear is that by removing zinc oxide, ETEC will spread, and no alternatives are available on the market!

A treasure hunt for phages infecting ETEC

In our group (PHAGEBio), we are huge phage supporters! Maybe we are a bit naïve thinking that all problems can be solved with phages, but killing ETEC with phages has not been a completely crazy idea, since we convinced the funding agency Innovation Fund Denmark (BioPIGLET project) and then Europe (AVANT project) to support our research. In these two projects, we aim to formulate and take to the market a phage product against porcine ETEC.

Got the money, we celebrated (with cake, not pork) and we started working hard to find phages that could kill ETEC. I can hear you saying “Come on, ETEC are E. coli, how hard it can be to find phages?” Well, ETEC are stubborn. They are not sensitive to other phages previously isolated against E. coli, for example. With the help of many great students (Christoffer, Lene and Semeh, so far), we are screening more than 2000 enrichments to find lytic phages that could infect the ETEC strains in our collection.

Semeh is ready to screen for phages specifically infecting ETEC
Semeh is ready to screen for phages specifically infecting ETEC.

All that glitters ain’t gold

The first months of the project, we managed to isolate many phages. We were optimistic and confident that we could use many of them. Then we sequenced a bunch and we found out that 90% were temperate phages. Where are the temperate phages are coming from? Are they induced prophages from the ETEC or are they in the samples and we propagate them with the enrichments? To answer to this, we will compare the phage genomes with the genomes of 150 of the Danish and European ETEC strains that we have in our collection.

Christoffer with a phage to test against ETEC
Christoffer with a phage to test against ETEC.

This treasure hunt has been challenging so far, but thanks to our enthusiastic collaborators in the phage community, we will be able to dig more into the biology of ETEC and their relationship with phages – lytic and temperate. Hopefully, we will also be able to propose a phage cocktail as an alternative to zinc oxide to save Christmas traditions in Denmark. Stay tuned!

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In collaboration with

Mary Ann Liebert PHAGE

Supported by

Leona M. and Harry B. Helmsley Charitable Trust

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