The terrifying specter of pandemic superbugs has loomed in the public consciousness for years, thanks to a barrage of warnings by public health experts on the increasing antibiotic resistance among pathogenic bacteria.
Yet the same phenomenon has also been occurring among species of pathogenic fungi, albeit a bit farther out of the spotlight.
Now, following the alarmingly rapid emergence of multi-drug resistance in many previously controllable human and crop plant-targeting strains, the scientific community is issuing a rallying cry.
Writing in a special issue of Science, an international team of researchers declared:
“To avoid a global collapse in our ability to control fungal infections and to avoid critical failures in medicine and food security, we must improve our stewardship of extant chemicals, promote new antifungal discovery, and leverage emerging technologies for alternative solutions.”
“Today, crop-destroying fungi account for perennial yield losses of ~20% worldwide, with a further 10% loss postharvest. Fungal effects on human health are currently spiraling, and the global mortality rate for fungal diseases now exceeds that for malaria or breast cancer and is comparable to those for tuberculosis and HIV.”
Fungal infections are transmitted through microscopic single-cell spores that can survive for long periods of time outside of a host, lying dormant in soil or water and easily kicked up into the air.
Because the Earth is quite literally covered by fungal organisms, the human immune system has evolved pretty solid defenses against most internal intruders.
The real danger arises for people with compromised immune systems – AIDS patients, the elderly, and people on medications for organ transplants, for example – or lung diseases (spores typically invade through the lungs). Once inside the body, unchecked fungal cells invade other organs – including the brain – and induce deadly inflammation by excreting toxins.
There are currently only four classes of antifungals available to humans, and like bacteria, fungal species can quickly evolve resistance to drug agents because they reproduce rapidly and can transfer genetic material from one cell to another. Several strains of fungi that are present in high concentrations around the world are now resistant to all four.
So, how did this happen? The authors highlight that increased global travel and trade have brought native pathogens to new areas, thus spreading resistance genes. And the ever-increasing use of antifungals – both in agriculture and at-risk patients requiring long-term preventative treatment – has kicked the evolutionary selection pressure for resistance into high gear.
“The azoles are our frontline class of antifungals, but they’re also the frontline fungicide in agriculture,” lead author Matthew Fisher told The Independent.
“They’re absolutely everywhere, we spray hundreds of thousands of kilos across the UK countryside and we use enormous quantities in our patients.”
Furthermore, development of new antifungals has always been limited by similarities between fungal cells and our own. Finding a compound that harms them but not us is incredibly difficult.
To prevent the oncoming crisis, Fisher and his colleagues call for increased research into novel fungal treatments, such as immunotherapies and RNA interference, and expedited evaluation processes to get them to market faster. In the meantime, agricultural operations need to use low doses of combined antifungals, rather than single high-dose applications, to lower the resistance selection pressure. Though this will reduce crop yields in the short term, it is a small price to pay for a little more time in our war on spores.