The first antibiotic. Penicillin, was discovered by Alexander Fleming in 1928 and more than 100 compounds have been found since, but no new class has been found since 1987. In the meantime, germs are becoming less and less responsive to antibiotic drugs. It’s only a matter of time until we lose the arms race, most scientists agree, unless we find some novel antibiotics. In our search for new weapons against bacterial infections, fungi might be our best bet, a new study concludes.

The first antibiotic was made from the Penicillia fungus more than a hundred years ago. New research reveals that their potential for production of novel antibiotics is far from exhausted. Credit: Jens Christian Nielsen.

Penicillin is actually derived from Penicillium fungi, and when researchers from Chalmers University of Technology sequenced the genomes of nine different types of Penicillium species, they were struck by the wealth of chemical pathways that could potentially destroy bacterial infections. Another fifteen types of fungi were investigated and rendered similar results.

In total, the researchers found more than 1,000 pathways that could lead to the production of new bioactive compounds against bacterial infections. Amazingly, in 90 percent of the cases, they could also predict what the chemical product for the pathway might look like, i.e. the antibiotic itself. For instance, they identified which of the studied fungi could enable the production of yanuthone, a popular antibiotic. They also identified which fungi could produce new versions of the drug, as reported in Nature Microbiology. 

In other words, the study suggests that not only are fungi a good place to start if pharmaceutical companies want to improve existing antibiotics, these organisms can also lead to the production of new antibiotics altogether. And who knows, maybe a new class of antibiotics — one that bacteria haven’t had the chance to catch up with — could be produced out of fungi. That would be immensely positive. Everyone knows we desperately need such a solution.

Antibiotic resistance is threatening to undo more than a century’s worth of medical progress. Each year, 25,000 patients from the EU and 63,000 patients from the USA die because of hospital-acquired bacterial infections which are resistant to multidrug-action. Financially, billions of dollars are lost each year due to multidrug-resistant bacterial infections. The trend is only set to become worse until a dangerous tipping point is reached where bacteria might become totally immune to the drugs we throw at them. Already, some doctors say that gonorrhea, until not too long ago a benign STD, might become untreatable in the coming decade. There was a time when simple bacterial infections, the kind we nowadays treat in a couple of days, were lethal. If we’re not careful, mankind risks reverting to this status quo.

“It’s important to find new antibiotics in order to give physicians a broad palette of antibiotics, existing ones as well as new ones, to use in treatment. This will make it harder for bacteria to develop resistance,” explains Jens Christian Nielsen.

“Previous efforts to find new antibiotics have mainly focused on bacteria. Fungi have been hard to study – we know very little of what they can do – but we do know that they develop bioactive substances naturally, as a way to protect themselves and survive in a competitive environment. This made it logical to apply our research tools to fungi.”

Chalmers researchers are now exploring some practical pathways for the production of the yanuthone compound. They’ve developed a map that makes it easy to compare hundreds of genes for the evaluation of bioactive products which could be adapted for any species of fungi. The war against bacterial infections, however, requires concentrated action among all stakeholders. All our livelihoods are at stake, rich or poor, smart or dumb. Bacteria doesn’t discriminate.

“Governments need to act. The pharmaceutical industry doesn’t want to spend money on new antibiotics, it’s not lucrative. This is why our governments have to step in and, for instance, support clinical studies. Their support would make it easier to reach the market, especially for smaller companies. This could fuel production,” says Jens Christian Nielsen.