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 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.

But what type of AMPs?

What antibiotics do we need to replace?

Instead of blindly designing AMPs to kill any bacteria, we tried to make sure that we would produce something useful in the real world. 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.

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

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 humans, with the knowledge that antibiotic resistance can pass easily from animal to human pathogens.

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

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:

From these 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.

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.

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

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