New research in mice repurposes a drug used for blood disorders to starve antibiotic-resistant fungus of iron, thus halving the survival rate of the yeast.
The drug resistance crisis is so dire that some researchers have warned that we may soon return “to a pre-antibiotic era in which minor infections can once again become deadly.”
The Centers for Disease Control and Prevention (CDC) have categorized the current antibiotic resistance threats as “urgent,” “serious,” or “concerning.”
The CDC consider fluconazole-resistant Candida, which account for 3,400 infections and 220 deaths each year, to be a “serious” threat.
Candida albicans is a fungus that can cause oral thrush and denture-related stomatitis, among other infections, when it overgrows.
C. albicans also ranks as the fourth leading cause of bloodstream infections acquired in the hospital, says Mira Edgerton, Ph.D., co-lead author of a new study that details an innovative way of stopping Candida infections.
The scientist, who is also a research professor in the department of oral biology at the University at Buffalo School of Dental Medicine, in New York, adds that there are currently only three major classes of antifungal drugs and that no new antifungal classes of drugs have appeared in decades.
“In the absence of novel drug candidates, drug repurposing aimed at using existing drugs to treat diseases is a promising strategy,” adds Prof. Edgerton.
The team published their findings in the journal Antimicrobial Agents and Chemotherapy.
The authors explain that C. albicans is the most prevalent fungus in the oral microbiome and that it relies on saliva to get the essential nutrients that it needs for survival.
C. albicans needs iron, specifically, to produce energy and repair its DNA. Iron is also the second most prevalent metal found in saliva.
In the new research, Prof. Edgerton and the team gave deferasirox — a drug that treats blood disorders — to mice with C. albicans. The drug works by lowering iron levels. Thus, it starved C. albicans of the essential nutrient that it needed to sustain the infection.
The scientists compared the effects in the mice that had received the treatment and a group that hadn’t.
They found that, in the deferasirox group, C. albicans had only a 12 percent survival rate, whereas the fungus had a 25 percent survival rate in the rodents that did not receive deferasirox.
The researchers suggest that this is because C. albicans became more susceptible to oxidative stress.
Additionally, in the mice that had received deferasirox, C. albicans had altered expression of 106 genes that are involved in iron metabolism, adhesion, and response to host immunity.
Sumant Puri, Ph.D. — also a co-lead researcher in the study and an assistant professor at Temple University’s Kornberg School of Dentistry, in Philadelphia, PA — says that this study is the first to find that iron starvation alters the gene expression of C. albicans during a live infection.
The scientist adds that the adult mouse model found that treatment with deferasirox does not cause iron deficiency, suggesting that the drug could be used as a preventive treatment.