More than a billion people get infected with a fungus annually. Despite being generally benign, these infections cause the deaths of over 1.5 million patients each year. The discovery of fungal infections strains that are resistant to one or more of the available medications is increasing, but recent years have seen a virtual halt in the development of new medications. Only a handful of clinical trials using brand-new active agents are being conducted right now to treat fungus infections. Lead author of the study, Dr. Angelo Frei of the Department of Chemistry, Biochemistry, and Pharmacy at the University of Bern, says, “This is an exceptionally small number compared to more than a thousand cancer drugs that are currently being tested on human subjects.” The JACS Au journal has published the findings.
Boosting antibiotic research with crowd sourcing
The Community for Open Antimicrobial Drug Discovery, or CO-ADD, was established by researchers at the University of Queensland in Australia to promote the development of anti-fungal and antibacterial agents. The initiative’s ambitious goal is to discover new antimicrobial active agents by giving chemists around the world the chance to test any chemical compound against bacteria and fungi for free. Frei says that at first, CO-ADD focused on “organic” molecules, which are mostly made of carbon, hydrogen, oxygen, and nitrogen and don’t have any metals in them.
Frei, whose research team at the University of Bern is working to create new metal-based antibiotics, discovered that more than 1,000 of the more than 300,000 compounds examined by CO-ADD contained metals. Most people experience a sense of unease when the word “metal” is used in conjunction with the word “people.” There is a widely held belief that metals are inherently bad for us. This is only partially accurate, though. Which metal is used and in what form are the deciding factors, “Frei, who is in charge of all the metal compounds in the CO-ADD database, explains.
Low toxicity was demonstrated.
The focus of the researchers’ latest study was on metal compounds that demonstrated activity against fungi. Here, various resistant fungus strains were tested against 21 highly active metal compounds. Cobalt, nickel, rhodium, palladium, silver, europium, iridium, platinum, molybdenum, and gold were among the metals present in these. According to Frei, “Many of the metal compounds showed good activity against all fungal infections strains and were up to 30,000 times more active against fungi than against human cells.” The most effective substances were then examined in wax moth larvae, a model organism. According to the researchers, only one of the eleven tested metal compounds exhibited toxic effects, and the other ten were well tolerated by the larvae. The next step involved testing a few metal compounds in an infection model, and one of them was successful in lowering the fungal infection in larvae.
Significant potential for widespread application
Medicine has long used metal compounds; one of the most popular anti-cancer medications is cisplatin, which contains platinum. Even so, there is still a long way to go before new metal-containing antimicrobial drugs can be approved. According to Frei, “our work is intended to enhance the reputation of metals in medical applications and inspire other research teams to further investigate this substantial but understudied field.” If we use the periodic table to its fullest, we might be able to avoid a time when there are no effective antibiotics or active agents to stop and treat fungal infections.
