Leaving no stone unturned in the fight against drug-resistant diseases

Drug-resistant diseases are on the rise, threatening to undermine our ability to treat serious illnesses.

Patricia-Ann Young speaks to Dr Mostafa Rateb of the University of the West of Scotland about his research and how he and his team go to the ends of the earth to discover new treatments.

Why are microorganisms so important to drug research?

Most antibiotics have been discovered in nature. Microbes have the power to produce really diverse compound structures that no synthetic chemist could create themselves or even think of.

Most antibiotics nowadays are either microbial natural products or inspired by microbial molecules. Scientists may do some modification on the compound to increase its bioavailability or lengthen its time of life, but the core compound they are working from has usually come from nature.

Microorganisms are superior to plants and marine organisms as they can produce large quantities in a small place. You must harvest many trees to get one gram of Taxol, an ingredient that helps treat cancer. We can now do it with a fungus in a lab and produce 10-20 grams of Taxol, which is quite a difference. In terms of environment, economy and cost effectiveness, microorganisms are really useful.

Can we not create our own healing compounds in labs?

Synthetic compounds are derived from human thinking, but microbes are much cleverer than us. In 2010 while doing my PhD studies at the University of Aberdeen, I isolated a complex compound that took around two months to identify and confirm its structure. In 2012, I moved to Florida and met a group of scientists that had been working to fully synthesise my 2010 compound. It took them around two and a half years to recreate the compound in the lab.

If you find the bacteria and have it in front of you, you can experiment and try to do some genetic engineering and discover results quickly. Bacteria can do so much in a short time that scientists would take months to recreate on their own.

Why are some healing microbes hard to find and harvest?

The active ingredients of many plants and microbes are different from place to place and/or time to time. Sometimes if you collect them in the winter, they have different active ingredients than they do if you collect them in the summer. Sometimes they can be different from morning to evening. When we find and harvest them, we must mimic their natural environments as closely as possible in our labs, which is not always easy.

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Why are you searching for organisms that grow in remote and/or harsh environments?

We have partners that collect microbes from a variety of places, such as salt lakes, deep sea areas and deserts. These organisms can survive under intense or harsh conditions and can produce metabolites that can protect themselves against the harsh conditions through natural selection.

These ‘hard to reach’ microbes are structurally diverse from those that are more commonly available and that are already widely used in modern medicine. Nowadays, drug-resistant diseases are a big problem, because previously treatable diseases are developing immunity to commonly used medicines.

We are searching for hard-to-find microbes because their novelty means that drug-resistant diseases will not have encountered them yet, and so they will not have the ability 
to produce resistance against their novel mechanisms, at least for a while.

How do you decide where to look for these rare organisms?

We try to select places that no one has reached before. We have collected samples from the Mariana Trench, the deepest place in the world. We often don’t expect life to be in these places, for example, samples were taken from the Atacama Desert in Chile, where no one expected life to exist at all. After a lot of work, we were able to prove, with the help of the great microbiologist, Professor Michael Goodfellow, that these organisms exist. We managed to isolate about 70 microorganisms from different locations in the desert, with some of them producing very nice antibiotics against multidrug resistant Staphylococcus aureus (MRSA), in collaboration with Professors Marcel Jaspars and Rainer Ebel.

By 2021, we had discovered very efficient anti-viral agents from three edible plants located in the Middle East that were effective in treating Covid-19. In 2022, we patented one of them as a natural compound that can successfully inhibit Covid.

Some are opting for ‘natural’ medicines over traditional treatments. What is your view?

While a compound is natural, it can be toxic. Everything we do is through the proper route and is fully studied and approved. Often people do not know how plants behave, or if they also contain toxic compounds too. Everything has to be regulated properly, from dosage to how the medicine is administered. People shouldn’t read research about a certain plant or microorganism and jump in and use it. We do not recommend that people go against the advice of their doctors in terms of treatment, especially for illnesses as serious as cancer.