The solution to antibiotic resistance might be under our feet: Finding unknown antibacterial compounds in soil

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Biologist Nataliia Machushynets felt like she was "looking for a needle in a haystack," trying to find new antibiotics to help solve the problem of resistance. During her Ph.D. research, she did find what she was looking for, in the soil beneath our feet.

The search for new antibiotics has slowed significantly in recent years, despite the urgent need for solutions. The World Health Organization (WHO) has created a priority list of resistant pathogens that require immediate attention. This decline in discovery contrasts with the "golden age" of antibiotic development in the 1950s, when nearly 70% of the antibiotics in use today were first identified.

Luckily, many new and potentially stronger antibiotics are still waiting to be discovered. They might be hiding right under our feet, Machushynets explains. Every gram of soil contains billions of microorganisms, which are a potential source of compounds that can kill bacteria. She calls them "nature's medicine makers."

Identifying the promising new compounds

During her Ph.D., under supervision of Gilles van Wezel at the Leiden Institute of Biology, Machushynets set out to find unknown antibacterial compounds capable of killing resistant pathogens. She says many compounds in the soil are already known or have proven ineffective. The challenge lies in identifying the promising new ones.

To avoid repeatedly finding the same compounds, Machushynets used a combination of innovative tools. This toolbox makes her research quite exceptional. Among other methods, she used bioinformatics to analyze the bacterial genomes.

DNA sequencing opened a whole new world of possibilities, she explains. "It made us realize we've barely scratched the surface of what bacteria are capable of producing. Current estimates suggest we know less than 5% of their potential."

By using a technique called MS-based metabolomics, Machushynets was able to identify promising compounds in the samples she examined. The combination of techniques she used is showcased on a platform called nanoRAPIDS, developed together with her colleague Isabel Nuñez, which allows other researchers to build on her work.

In the footsteps of pioneering female biologist Balbina Johnson

One of the interesting antibacterial compounds Machushynets discovered during her Ph.D., is called paenitracin. It has a special meaning for her, as it is a new variant of bacitracin. Bacitracin was first discovered by the pioneering female researcher Balbina Johnson. Johnson isolated the bacteria that produces this compound from the wound of a little girl named Tracy—hence the name bacitracin.

Machushynets says, "It's empowering to show it's still possible to discover new things."

The potential to make a real impact

Since arriving from her home country of Ukraine in Leiden in 2015 to pursue her master's degree, Machushynets has been trying to make a difference through her work. Beyond her research, she made a difference through social action, organizing a campaign in 2022 to collect essentials supplies for babies in Ukrainian hospitals.

Although her research is still in the "discovery phase" and many steps are needed to optimize these antibiotics for practical use, every new finding holds the potential to make a real impact. "It's something that truly inspires me, knowing that your work can actually be used to solve problems," she says.

More information: Thesis, Expanding the chemical space of antibiotics produced by Paenibacillus and Streptomyces: scholarlypublications.universi … /handle/1887/4082475

Provided by Leiden University