Discovery Of Antibiotics From Marine Microbes [Interview with Katherine Duncan]

Imagine a world where common infections become deadly once again. This isn’t science fiction; it’s a looming threat due to the rise of antibiotic-resistant bacteria. But there’s a glimmer of hope in the vast, unexplored depths of our oceans.

Dr. Katherine Duncan, a marine microbiologist, is on a mission to discover new antibiotics from unique ocean microbes. This interview dives into the fascinating research Dr. Duncan leads at the Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde in Glasgow, UK, and the potential of marine microbes to combat antibiotic resistance. You’ll learn:

• Why traditional methods of antibiotic discovery are running dry
• How extreme environments like Antarctica and the Arctic harbor unique microbes
• The challenges and rewards of isolating and studying these microbes
• The future of biodiscovery and the exciting possibilities it holds

Read on to discover the secrets hidden within ocean microbes that could revolutionize medicine.

Question: Tell me a little bit about what you do and what you’re trying to accomplish with your research.

Answer: I have a team of PhD students and postdocs, and all of the research is marine microbiology. We look at bacteria and microalgae from the oceans. The overarching theme is what chemistry is produced—the term for this chemistry is natural products or specialized metabolites.

One of the avenues that we look at is drug discovery, and in particular, antibiotic discovery, because we know that we need new antibiotics because of rising antibiotic resistance.

We’re also interested in the role of this chemistry in the environment and how the environment  (salinity, nutrients, pressure, location, etc.) influences the chemistry.

The “golden age” of drug discovery was from the 1930s to the 1970s, and a particular group of bacteria, called Actinobacteria, were prolific at producing specialized metabolites. Many of these have applications in human health, including antibiotics we use every day, even now. However, in the 1970s re-discovery of known chemistry was problematic, resulting in a lack of new molecules being discovered. One of the things that we can do to circumvent this problem, which still exists today, is to isolate strains from different environments.

Bacteria evolve really quickly, and they’re influenced by their surrounding environment. Unlike humans—we inherit our DNA vertically (acquire our genetic abilities from our parents and then pass them to our offspring)—bacteria can swap their genes horizontally, meaning the environment they’re in really influences the kind of chemistry or genes that they acquire.

The oceans have only been looked at really, since the 1970s with the advent of scientific scuba diving. The oceans cover an incredible 70% of the Earth’s surface, and there’s a huge amount of environmental pressures that don’t exist on land.

There are invertebrate species that exist in oceans that aren’t on land, like sponges and coral, for example. But there are also bacteria that exist in the oceans that don’t exist on land. For example, Salinispora (actinomycetes), which requires seawater for growth, so it’s obligate marine.

The other thing that we know is that the pressures and environment that these bacteria are under is totally different from land, so that can really influence chemistry. As a result, we’ve been looking at some strains from Antarctica and the Arctic because they’re under completely different environmental pressures than we would see on land.

Question: Have you found antibiotics or microbial strains in Antarctica and the Arctic that you can’t find anywhere else?

Answer: Yeah. This is unpublished, so I’m not going to reveal too many details, but we’ve isolated, what we believe are, new species of bacteria from Antarctica, and sequenced their genomes. All of the bacteria have biosynthetic gene clusters (genes that code for the chemistry) that seem very different from modern-day bacteria, and so does the chemistry. So we’re pretty excited about that.

Question: Do you think there’s a reason why you would find more interesting microbial chemistry in the cold, in particular, versus hot?

Answer: So, I guess, I don’t really think it’s a direct comparison. The tropical regions are widely known, even from the Darwin days, as being hotspots of biodiversity. And with biodiversity, you get chemical diversity, per se. Bacteria from cold waters are understudied, so the chance of finding something new is probably greater.

When you compare cold versus tropical waters, the whole environment (all the species that they will be in contact with and the nutrients and abilities) will be completely different from that of temperate and tropical waters. So, I think it’s quite exciting to look at.

And very little research has been done in cold water because everyone likes to scuba dive in a warm location. There’s been some pioneering work from labs in Norway and Canada in temperate waters that have isolated some pretty cool strains that produce new metabolites as well.

Question: Do some of the strains prefer to grow in the cold over room temperature or body temperature?

Answer: The bacterial strains we isolate may not necessarily be evolved to grow at those temperatures—they may be just existing as spores (in an asleep state). We’ve done some preliminary studies, and they grow slowly at room temperature. For the student working on those cold strains at the moment, it already requires a lot of patience—it takes months.

From a biodiscovery point of view, it’s always exciting to go to understudied locations. But the important point to note is that those underexplored locations don’t have to be as extreme as Antarctica.

It’s about going a bit further in terms of biodiscovery, rather than your doorstep. But there are still some potentially exciting discoveries at your doorstep.

Question: How long have you been working on the Antarctica project, and how did it start?

Answer: Maybe 3 years. And it’s actually in collaboration with the Scottish Marine Institute, where I used to work and in collaboration with a researcher called Professor John Howe, who is a biogeochemist. They collect sediment cores to look at the inorganic content. I had a discussion with him and thought it would be quite interesting to attempt Actinobacteria isolation from the sediment cores.

We can do a lot with the strains that we already have from culture collections as environmental microbiology labs often have freezers full of strains from various places. However, they were maybe initially looked at when we didn’t have the technology available to us today, including tools to do comparative ‘omics analysis. 

I think having well-curated culture collections that can be revisited with ‘omics tools is quite exciting.

Then bearing in mind that, even with all the bacteria we have isolated, even really well-studied bacteria, we typically can only see about 10% of their chemical potential. As they have sometimes more than 30  biosynthetic gene clusters, but in reality, we can see about 10% of the products of those genes. This is why I think we need to understand more about the ecological function of the specialized metabolites, i.e., why the chemistry is being produced in the environment.

To uncover the full chemical potential of these bacteria, a good strategy would be to simulate their environmental conditions.

Question: Would you be able to take the biosynthetic gene clusters out and express it in E. coli? Or is it too laborious to do that with all of those clusters?

Answer: I don’t do synthetic biology, but I work with people that do, and I think that heterologous expression of biosynthetic gene clusters from Actinobacteria has been successful, especially with new tools like CRISPR-Cas. However, the gene clusters tend to be quite big because they are clusters, and optimization is often strain and metabolite specific. It will be exciting to follow these developments, as there has already been some significant progress in this area.

Question: Okay, so it’s still hard to do. And you’re saying it would probably ultimately be easier if you could get the bacteria to do it instead, is that right?

Answer: These metabolites are extremely complex and take many steps to make (biosynthesis). But bacteria have already got this sorted. If we can harness their ability, and understand why bacteria produce the chemistry in the first place, then we’ve got a much better chance of accessing more of it. 

Bacteria are far better chemists than we’ll ever be. 

Question: What is the thing that you’re most excited about coming up in your lab?

Answer: I’m excited because I’ve just got a Centre for Doctoral Training funded that’s in antimicrobial resistance in collaboration with collaborators from biomedical engineering and electrical engineering. The new PhD students will research diagnosis (how we can detect what bacteria are present quickly), measuring antibiotic effectiveness, and new angles for antibiotic discovery. It’s truly interdisciplinary in nature.

My lab is at the interface of microbiology and chemistry. I think that’s the new frontier, if you will, for discovery. By having these physical techniques, we can understand the biological world better. 

I think that the interface of physical sciences with biological sciences provides an incredible insight into this microscopic world.

Not many people can say they discover things for a living. To be able to be the first person that has isolated and studied an organism, in this case, a microorganism is a great privilege.

And the oceans are so understudied and currently, the field of marine natural products is quite small. If you think about how big the oceans are, how deep they are in places like the Mariana Trench, and how complex they are, there is so much still to discover.

Key Takeaways:

• The discovery of marine natural products, especially novel antibiotics, from microorganisms is a new and exciting research area.
• Dr. Duncan’s lab is conducting interdisciplinary research to discover novel antimicrobials from marine microorganisms.
• Microorganisms are excellent chemists.
• The chemistry is greatly influenced by the environment.
• Using advanced technology to investigate marine bacteria—even from historic strain collections—will provide insight to tailor future biodiscovery efforts.

To learn more about Dr. Duncan and her research group, you can visit her website and follow her on Twitter.