How Starving Fungus of Iron May Treat Drug-Resistant Infections

A study published in Antimicrobial Agents and Chemotherapy details how starving Candida albicans of iron can potentially prevent drug-resistant infections. The findings suggest reducing host iron levels can reduce the severity of oral yeast infections, such as oropharyngeal candidiasis (thrush), and may lead to the development of new preventive treatments.

The U.S. Centers for Disease Control and Prevention (CDC) calls antibiotic-resistant pathogens “one of the biggest public health challenges of our time.”¹ The center estimates that each year at least 2 million Americans experience an antibiotic-resistant infection, and at least 23,000 die. The threat makes finding ways to combat antibiotic resistance—including this most recent study—vital to thwarting the spread of these bacterial infections.

In the study, “Iron Chelator Deferasirox Reduces Candida albicans Invasion of Oral Epithelial Cells and Infection Levels in Murine Oropharyngeal Candidiasis,” researchers at Temple University in Philadelphia, and the University at Buffalo School of Dental Medicine in New York, evaluated the role of iron in reducing fungal growth.

“Iron is an essential nutrient that plays a role in a plethora of metabolic processes, including sugar metabolism, energy production, and DNA replication. During infections, yeast cells proliferate actively within the host, creating an elevated need for this metal,” explains Mira Edgerton, DDS, PhD, a research professor in the Department of Oral Biology at the University at Buffalo School of Dental Medicine, and co-lead author of the study.

Investigators gave deferasirox—a drug that works by reducing iron levels—to mice with C. albicans. Comparing the effects in subjects who had received the treatment and the control group, investigators determined C. albicans had a 12% survival rate in the deferasirox group, whereas it had a 25% survival rate in the subjects that did not receive the drug. “These findings indicate that an elevated iron level may promote more severe disease, thereby suggesting that preventing excess iron in the body may help keep these infections at bay,” says Edgerton. “A key finding was that iron-starved fungal cells well not able to invade the oral epithelial cells.”

Additionally, C. albicans had altered expression of 106 genes involved in iron metabolism, adhesion and response to host immunity in the mice that received deferasirox. Iron deficiency was not experienced in this mouse model, indicating deferasirox may be used as a preventive treatment.

Patients with oropharyngeal candidiasis typically experience mucosal pain, taste alteration, dysphagia, and oral malodor. This condition often presents in older adults and patients undergoing cancer therapy. The bacteria also contributes to denture stomatitis.

In order to effectively protect themselves and their patients, dental teams should be aware of the many symptoms of thrush, and understand how antibiotic-resistant infections are spread through both direct and indirect contact.

“Aside from existing guidelines, oral health professionals may enquire about the patients’ blood iron levels and advise them to avoid iron-rich foods and especially taking any iron supplements, if the levels are high,” Edgerton says.

REFERENCE

1. US Centers for Disease Control and Prevention. Antibiotic/Antimicrobial Resistance: Biggest Threats and Data. Available at: https://www.cdc.gov/drugresistance/biggest_threats.html. Accessed July 11, 2019.