How do we minimize the use of antibiotics?

Frédérique Le Roux Credit: Amélie Philibert, Université de Montréal
Frédérique Le Roux Credit: Amélie Philibert, Université de Montréal
New to UdeM and flush with an $8M, federally funded research chair, microbiologist Frédérique Le Roux looks to solve the problem of infectious diseases of bacterial origin in farmed marine species.

In the mid-2010s, while studying diseases in farmed oysters in her native Brittany, French microbiologist Frédérique Le Roux had a professional wakeup call: there was a close link, she realized, between the emergence of pathogens and the quality of the environment. In her seaside laboratory at the Roscoff Biological Station she saw how anthropization - adaptation to human activity - was impacting the health of marine life.

"When you work on pathogens in marine species, you can see the emergence of diseases caused by man - and, as a microbiologist, you think about what can be done to remedy the situation," she explains.

"In the short term, technicians try to boost the quality of production, and regulations can aim to ensure that, when they occur, diseases remain confined to a geographical area - through better detection of pathogens and a ban on transfers between farms, for instance.

"But as a microbiologist, or more precisely a bacteriologist, I had to look at the big picture and ask myself about the overuse of antibiotics in those farms: how can we simply avoid using them altogether?"

Her question led her to a new area of expertise - bacteriophages - and it’s one she’ll explore in detail now that she’s moved to Montreal and taken up a position as a professor of microbiology at Université de Montréal. Flush with a $8-milllion, federally funded Canada Excellence in Research Chair, she and her team of scientists will spend the next eight years investigating vibrios, the most common bacteria killing aquacultured marine species - specifically, oysters.

Bacteriophages are ubiquitous natural viruses that infect and reproduce themselves inside bacteria, and have begun to be used in medical practice and in agronomy as an alternative to manmade antibiotics. Le Roux sees their vast potential in aquaculture, too.

"Working on bacteriophages before I came here was in part a response to concerns I was having about changes in our environment: how could we promote sustainable development and, in particular, ecological alternatives to antibiotics?" she recalls.

’Improving our life on Earth’

"Alongside changes in my personal lifestyle - I now sort my waste, practice flexitarianism, cycle to work, and moved into a small flat - professionally I’ve concentrated on work that’s likely to improve our life on Earth," Le Roux says.

In particular, that has meant diving deeper into an area she knows well: the coastal marine environment, increasingly weakened by overfishing and the intensification of agriculture and aquaculture.

"People have a tendency, if something works, to want to produce more of it to make more money," Le Roux points out.

"Take shrimp, for example: I worked on shrimp production in New Caledonia [France’s overseas territory in the Pacific Ocean, east of Australia], where the industry did very well in the first 10 years, before a bacterial epidemic hit and wiped out 90 per cent of the population. Or Ecuador: I was there a few months ago, and same thing; Ecuador was the world’s second-largest producer of shrimp until everything collapsed because of a virus brought in from Asia. These epidemics also highlight the need to more quickly diagnose pathogens that develop when sea creatures are transported without proper health controls in place."

Daughter of a Breton ocean fishing family, Le Roux comes from the Atlantic port of Le Guilvinec , famous for its langoustine fishery. "Not that that leads a person to go on to become a scientist," she points out. "In fact, believe it or not I always wanted to go into the fine arts! But my mother insisted I pursue a career in the sciences, and as it turns out, she was right. During my first year of university, I discovered my passion for microbiology."

’The best models’

She was interested in germs, molecular biology, DNA, "and the best models in molecular biology have always been viruses: despite their simplicity, they are remarkably ingenious, and I wanted to learn more about them. And for my doctoral thesis, I worked on a human herpes virus, the Epstein Barr virus, and its interaction with cancer. Despite growing up by the sea I wasn’t at all predisposed to study marine biology, but in the end, after my first postdoc [at the Institut Gustav Roussy cancer-research hospital, in Paris], that’s what I did."

In 1998, Le Roux seized the opportunity to work at IFREMER , the Institut français de recherche pour l’exploitation de la mer. "I started to look at diseases in seafood farms: parasites affecting mussels and oysters and such," she recalls. "And that became my research project, on bacterial pathogens in shellfish - vibrios - and I spent the next 20 years doing that at IFREMER."

Why decide to work on marine species in aquaculture? "At the end of the 90s, there was a lot of competition for research funding in human biology, cancer and infectious diseases," Le Roux recalls. "In the environmental sciences, there was a lot to do. Back then, there were no molecular tools and no models for studying diseases, and esearch into public, animal and environmental health was compartmentalized.

"What attracted me was the idea of being a pioneer in research into pathogens in nature, and my skills in molecular biology proved very useful for this."

The world was her oyster, so to speak. After IFREMER, she spent 2004 to 2008 at the Institut Pasteur in Paris, analyzing vibrio genome and developing the many genetic tools she still uses today, and in 2008 crossed two oceans as a guest researcher at the Harvard Medical School and for short stints at the IFREMER station in New Caledonia, where she completed her work on pathogenic vibrios in shrimp. Then, four years ago, Le Roux found her new calling: bacteriophages. But things didn’t go quite as she planned.

"We won’t go into detail about everything that bugs me about France, but the short answer as to why I left is that where I worked was just too far-removed from my area of research. Sure, it had its advantages: I was right on the ocean, could sample the many microbes I needed for my research, and had a close relationship with colleagues working on the ecology and evolution of environmental organisms.

"But the disadvantage was that in my lab I missed interacting with my peers; I was the only molecular biologist there working on phages and bacteria. Most of my colleagues were in Paris, four hours away from the coast by TGV. I’d reached a dead-end in being able to develop the molecular side of my research, and I was having a lot of trouble recruiting PhD students and postdocs to my team."

Montreal beckons

That’s when UdeM came calling.

Through professors Marylise Duperthuy and Yves Brun , Le Roux heard about a federal competition to attract leaders in their fields to Canada, and an opportunity at the Faculty of Medicine for a professorship in microbiology. And since she was looking anyway (and had even been offered a position at the Université Aix-Marseilles/CNRS’s Laboratoire de chimie bacterienne ), she decided to learn more in a series of Zoom meetings that began in October 2021 and concluded in March 2022, when she flew to Montreal to meet her colleagues here in person.

"My first impression? I was fascinated by the technical means at my disposal, UdeM’s network of affiliated research centres, its equipment, its research teams, all the cross-disciplinary work that’s possible here, and the wide diversity of Canadian and international students you have," she recalls. "There’s a kind of wind in the sails here that reminds me of the energy I felt in my two years in Boston."

Her work aligns perfectly with the basic science priorities of the medical faculty and the "host-pathogen-environment interactions" branch of research at newly opened Centre for Biomedical Innovation , points out the faculty’s vice-dean, Ekat Kritikou.

It’s Montreal’s entrepreneurial spirit in science that really pulled Le Roux in.

"I’m very attracted by the way of going about scientific research here: the freedom, the flexibility, the confidence, the dynamism. France is great if it’s stability you’re after. Here, life is a lot riskier but also provides more challenges, if you want them. I left my permanent position in France behind, along with my fully equipped laboratory, and arrived alone in Montreal as a new professor at UdeM. I’m starting from scratch but with $8 million and eight years ahead of me. It’ll be an adventure!"

Returning to UdeM last December, she went over renovation plans for her sixth-floor lab in the Roger-Gaudry building. And in August, she moved here permanently, renting a street-level condo near the university’s MIL Campus, in MileEx, not far from the Jean-Talon Market where she likes to stock up for the cooking she loves to do in her new place. Her daughter Zoë, 24, moved here a years ago and works nearby at the French gaming firm Ubisoft, where she’s employed as a graphic artist.

Building a new team

In France, Le Roux left behind a small team ranging between five and 10 staff and researchers, and she’ll try to replicate that here, hiring three staffers by the end of this year (one to help set up her lab, another for technical support, and another to manage bioinformatics), and intending to liaise with a research lab in Rimouski and Vancouver, and also reaching out to other phages specialists such as Sylvain Moineau at Université Laval in Quebec City and Karen Maxwell at the University of Toronto.

In the meantime, she busies herself in her new apartment, which she’s decorated with souvenirs from her travels (textiles from Burkina Faso, large Indonesian shadow puppets on the floor) small paintings she’s done herself, a bookshelf of DVDs (Almodvar, Tarantino, Guédiguian), and an oversize Charlie Hebdo book propping up one end of her small library. Keeping her company, her dog Darwin, a 9-year-old Cavalier King Charles, snores audibly through her many video conferences.

By the entrance stands the folding bike she brought from France - and this prompts one rare negative comment about her adopted city.

"Have you seen all the potholes - and how people drive?" Le Roux exclaims. "I’m going to have to buy a helmet!

About this CERC

Eco-Evo-Patho of Microbes in Nature

Frédérique Le Roux, Microbiology, Université de Montréal Antibiotic resistance is one of the biggest threats to global health. Bacteriophages, which are the natural predators of bacteria, are now seriously considered as alternative therapies to antibiotics. This CERC aims to explore antibiotic resistance in marine bacteria and interaction between these bacteria and their bacteriophages.

Vibrios, which encompass human and animal bacterial pathogens, will be used as model systems, favoring translational research as part of the "One Planet - One Health" priority area.

Based on a unique collection of environmental isolates, the diversity, mechanisms and evolution of antimicrobial resistance (antibiotic and heavy metal) will be explored. The lab will seek to understand genome size heterogeneity in natural populations of vibrio and test the hypothesis that oysters and Canadian giant clams function as a hot spot for horizontal gene transfer.

The mechanisms involved in the coevolution of bacteriophage and bacteria in nature will also be explored, as well as how coevolution affects the specificity of the bacteriophages and the pathogenicity of the bacteria.

This work will help evaluate the feasability of using phage therapy as an alternative to antibiotics.