Gutting to chase on how bacteria adapts and functions

Monash Lens

Dena Lyras has spent her professional life trying to understand a complex and formidable enemy – antibiotic-resistant bacteria, particularly those that proliferate in the human gut.

  • Dena Lyras

    Professor, Microbiology, Monash Biomedicine Discovery Institute

Her efforts have been rewarded with a $3.3 million ARC Laureate fellowship – “Understanding how bacteria adapt and function in the complex gut ecosystem”.

She’s the first female ARC Laureate fellow in Monash University’s Faculty of Medicine.

The professor of microbiology has had a successful career – she has her own laboratory at the Monash Biomedicine Discovery Institute, where she’s deputy director, and she serves as Australian Society of Microbiology president.

Microbiology fascinated her while she was a student at LaTrobe University. “My PhD was about antibiotic resistance, and how this resistance moves around between bacteria.”

She joined Monash University as a researcher in the early 1990s, studying antibiotic resistance in the human gut, particularly Clostridioides difficile, which is often contracted in hospitals, causing diarrhoea. In the years since, she’s observed C. difficile evolve – and successfully evade – stronger antibiotic treatments.

But when she first encountered the bacterium, she became curious about how it was able to survive in the gut at all.

“It started me down the road of studying the gut, and how bacteria grow in the gut, and that brought together this concept of antibiotic resistance, gut bacteria, and the environment in the gut. That’s what I study now.”

She describes the gut microbiome as “a really complicated ecosystem of microbes”, which she likens to a rainforest. The microbes and their host have a complex relationship, which, if allowed to flourish undisturbed, is crucial to human health, including our mental wellbeing.

Antibiotics destroy that ecosystem, similar to how a bulldozer razes a rainforest, she says. Antibiotics “don’t discriminate between microbes; they kill a large proportion of the microbes there”.

“But there are some microbes (including C. difficile) that can resist that antibiotic force, like little weeds that come through. And because there’s nothing else there, they take over.”

One reason antibiotic resistance appears in hospitals is because antibiotics are administered to hospital patients.

“Also, the hospital environment can become contaminated with these sorts of microbes, and so it becomes easier to catch them in that environment,” she says.

“But it happens in the community as well. It happens in animals. It’s a big problem in animals that are given antibiotics.” (How antibiotic-resistant microbes travel between domestic and farm animals and humans will form part of her research.)

Survival of the fittest

The main thrust of her ARC Laureate work aims to better-understand how microbes are able to survive in the gut.

“Think about what the gut does to our food. It’s aggressively breaking it down,” she says.

“Microbes have to find ways to live in there despite the fact that the host is constantly trying to kill them. They have had to adapt to function in that environment. I want to understand that. We understand a little bit of it, but not enough.

“And the microbes don’t just survive. They’re doing very well. They interact with each other. They pass on antibiotic resistance from one to the other. I want to understand how that happens, in that environment.”

Interest in the microbiome and the role it plays in human health has grown in the past five years, partly because researchers have more powerful microscopy tools, she says.

“These imaging tools allow us to see what these microbes look like when we take them out of the gut.

“Do they look the same as when we grow them in the test tube? Actually, our data suggests not quite. They’re probably somewhat different.

“Now, we can study those bacteria, how they’re interacting with one another, how they’re interacting with the gut tissue, and other factors in that complex space.”

Commercialising the research

Professor Lyras says “a lot of my work is discovery, true discovery, it’s curiosity-driven”, but she also works “with industry partners developing products to fight microbes, testing products to help in a hospital environment, for example, or treatments for infections”.

“I do both of those types of work. I don’t think you can have one without the other. You can’t come up with innovative new solutions without understanding the basics, because the pipelines run dry.”

Australia, unfortunately, “does not fund discovery science very well”, she says. “When I look at grant applications, more than 90% of them are wonderful science. Fantastic work. To think that only 10% or less of those applications will be funded is heartbreaking.”

Australia also needs to step up how it translates its scientific and medical discoveries into products that have practical applications, she says.

“Australian scientists have such intellectual capacity and such great ideas, but bridging that discovery science to get to the translation is not something we do well either,” she says.

COVID has shown us “how quickly a problem can arise, and how quickly we need to find solutions”.

Concern for teaching staff

Professor Lyras is a teacher as well as a researcher, and she’s concerned that 10% of university teaching staff lost their positions in the past year, as the loss of foreign students caused universities to tighten their belts.

“Our community has invested a lot of money in these people, and they have world-class skills. They’re going to fall out of the system,” she warns.

“Where will our next generation of teachers and researchers come from? We need excellent teachers to train the researchers who will find the solution to problems as they arise. I fear we’re breaking that critical pipeline in a way that is a deep loss to Australia and our capabilities.”

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