Microorganisms like bacteria and fungi are increasingly becoming resistant to our best drugs, which is hurtling us towards a terrifying future where once-easily-treated infections become potentially life-threatening again. In a new approach to this problem, researchers from the University at Buffalo and Temple University have tested an alternative to antibiotics that uses existing drugs to starve a fungal infection of vital nutrients.
The fungal species Candidas albicans is commonly found in the human mouth and gut, and most of the time it's harmless. But this opportunistic microbe has been known to flare up and cause yeast infections like oral thrush or denture-related stomatitis, and in extreme cases can find its way into the bloodstream with potentially deadly results.
The bad news is that like many other microbes, C. albicans is becoming more resist to antifungal drugs. Worse still, only three classes of antifungal drugs exist and they're all starting to fail, with no new ones ready to take their place. If nothing is done about the problem, this common infection could become far more lethal.
So the researchers on the new study investigated another approach. Rather than developing new antifungal drugs, the team found that existing drugs used for other purposes could instead be used against fungi through other means.
In this case, that drug was deferasirox, which is currently used to reduce iron levels in patients who may be "overloaded" with it. Since iron is an essential nutrient for C. albicans, the idea is that the drug will starve the fungus and keep the infection under control.
The team tested the technique by putting deferasirox into the drinking water of lab mice infected C. albicans. And the results were promising – iron in the saliva of treated mice was found to drop to 25 percent of normal levels.
The drug itself doesn't kill the infection, but with less iron available, the fungus' health suffers and makes it easier for the immune system to wipe it out. The team found that the treatment led to a two-fold reduction in the fungus survival rate – just 12 percent survived, compared to 25 percent in mice that weren't treated with deferasirox.
"In the absence of novel drug candidates, drug repurposing aimed at using existing drugs to treat diseases is a promising strategy," says Mira Edgerton, co-lead investigator of the study.
Interestingly, the researchers also noted that the expression of 106 genes in the fungus was altered, including about a quarter of them that are regulated by iron or have iron-related functions. These changes reduce C. albicans' ability to infect tissue.
Although mouse studies don't always translate to humans, these results should carry across relatively easily – after all, deferasirox is already in use in humans. Importantly, other studies have previously shown that the drug doesn't cause iron deficiency in people with normal iron levels, so it should be safe as a preventative measure in vulnerable patients.
The research was published in the journal Antimicrobial Agents and Chemotherapy.
Source: University at Buffalo
