Introduction

We are a team of scientists from diverse backgrounds and we started our project with the perspective of a researcher.
We understand the basic concepts behind the evolution of antibiotic resistance. Measures reducing antibiotic use will tend to reduce of antibiotic resistance. With this simple understanding, we decided to work on a technology to replace antibiotics.

We thought that Antimicrobial Peptides (AMPs) were simply cool! They have beautiful peptide structures and can be engineered by interesting methods.

Our advisors encouraged us to work on AMPs because they are small, easy to design and to test on bacteria - all the prerequisites to simplify an iGEM project.
These features led us to explore applications of AMPs as replacement antibiotics.

But what type of AMPs?

What antibiotics do we need to replace?

Instead of blindly designing AMPs to kill any bacteria, we assured that our product would be useful in the real world to solve . That means going outside the lab to meet with the real people who combat antibiotic resistance in the places where they work.

The Integrated Design section tells the story of how we went from “AMPs are cool” to a concrete project developing specific, nontoxic AMPs to treat Gram-negative infections in the piglet gut.

Results

France has a policy to reduce antibiotic resistance

Beginning in 2001, France has implemented a series of policies to combat the rise of antibiotic resistance. The overall goals could be summarized:

• To “reduce, replace and re-think” the use of antibiotics in humans and animals.
• To raise awareness of the problem among doctors, veterinarians and the public.
• To coordinate policy with other countries under the slogan “One World, One Health.”

We studied these policies, using them to frame our own research. From this, we learned about ECOANTIBIO, a national plan created by the Ministry of Health to reduce antibiotic use in livestock by 25% over five years. This program is coordinated with similar efforts to reduce antibiotic use in human doctors, with the knowledge that antibiotic resistance can pass easily from animal to human pathogens.

The policy goal to raise awareness was successful on us. Thanks to our study of existing French policy, we realized that the veterinary sector was a major priority.

Veterinarians confront antibiotic resistance in pigs

We reached out to our personal networks to find people on the front lines of antibiotic resistance. We traveled to Brittany, a major center of French meat production, and met with:

• Marc Quere, a retired veterinarian and writer.
• Paul Pfister, the CEO of a large veterinary practice.
• Benoît Quéro, a vet and the mayor of Plumeliau, a farming town.

From these any other veterinarians, we learned of the real-world challenges of treating antibiotics in piglets. Pork represents 46% of the meat consumed in France, making the pig industry a major consumer of antibiotics.

Piglets in particular are sensitive to digestive disease and easily die from them, so farmers treat infections aggressively. We decided to target piglet intestinal infections for our application.

The importance of E. coli and other Gram-negatives

Once we had decided to focus on pig intestine infections, we wanted more specific data about the pathogens and resistances at work. We attended the conference “Antimicrobial Resistance and Society” at the Institut Curie. There we met Jean-Yves Madec, scientific director of ANSES, the national food security agency. He confirmed for us that piglet gut infections are a major concern and that E. coli and other Gram-negative pathogens are the most common cause.

With his help, we obtained access to raw data from PORC 2017, a surveillance program for antibiotic resistance in animals. These data highlight amoxicillin and tetracycline as drugs with the most frequent evolved resistance. With this information, we knew which bacterial species we needed to target and which drugs we needed to replace.

Publishing our Work in The Conversation

Our research into the problem of antibiotic resistance brought us into contact with farmers, doctors, researchers and policy professionals all over France. Along the way, we befriended many good people from different domains, united by a common goal. We had even obtained an original, unpublished data set to study and analyze.
Thinking back to the original policy goals that motivated us, one of them was raising awareness and informing the public. We contacted The Conversation, a news magazine that specializes in making academic research accessible to the public. With help from their journalists and editors, our study of antibiotic resistance in France was published in both French and English.

Article : “Piglets, bacteria and antibiotic resistance: a dangerous combination for human health”[ PDF ]

Conclusion

Our work in Integrated Design lead us to the key features needed for our antibiotic replacement.

• An antimicrobial peptide
• to replace amoxicillin and tetracycline
• for killing Gram-negative E.coli
• in the piglet intestine
• with low toxicity to mammalian cells