Candida auris Hair Follicle Persistence and Immune Evasion

Candida auris causes roughly 3,000 deaths each year among patients in U.S. hospitals and long-term care facilities, according to federal health data, prompting researchers to investigate how this multidrug-resistant pathogenic yeast persists on human skin. While the fungus has been known to colonize the skin since its discovery in 2009, scientists have lacked a clear understanding of the biological mechanisms that allow it to linger despite immune defenses.

How Candida Auris Outcompetes Common Skin Fungi

To uncover these survival mechanisms, a team of researchers compared the pathogen against Candida albicans, a common fungus that the human immune system typically clears within days. According to findings published from studies utilizing mouse models, fungal and mouse genetics, immunology, single-cell RNA-seq, and volumetric quantitative confocal microscopy, C. albicans disappeared quickly while C. auris persisted by taking refuge inside hair follicles.

“Candida auris colonizes skin way better than most other fungi, setting it up to invade once the immune system is weakened,” said Dean Merrill, MD, a dermatologist and professor at UCSF. Merrill added that the primary clinical obstacle remains a lack of effective methods to remove the pathogen from the skin surface.

The Immune Response Triggered by Chitin Remodeling

Scientists found that mouse skin was colonized by C. auris with greater persistence and higher titers than C. albicans, showcasing a marked preference for hair follicles alongside direct hair-binding capabilities.

While C. albicans provoked a host-protective type 3/17 cutaneous immune response stimulated by interleukin-17A (IL-17A), C. auris instead stimulated an immune reaction skewed toward type 1.

This alternative pathway involved elevated production of interferon-γ (IFNγ) alongside an expansion around hair follicles of T helper 1 (Th1) immune cells, type 1 conventional dendritic cells (cDC1), and type 1 cytotoxic T cells (Tc1).

The investigators determined that hair follicle keratinocytes received direct signals from this IFNγ, which suppressed the downstream programs and gene expression driven by IL-17A that typically support antimicrobial defense and skin barrier integrity.

Cellular Nesting and Future Treatment Targets

By remodeling its exterior cell wall to expose more chitin, C. auris spurs immune cells to release interferon gamma around the hair follicle. This interferon gamma blocks the skin’s natural antifungal defenses while slowing the replacement of hair follicle cells. The resulting buildup of older, damaged cells creates a stable niche where the fungus can flourish.

“Chitin is widespread in nature, so it’s not like the human skin never encounters it, but we were surprised to see that C. auris actively uses its chitin to turn the skin into a perfect nest,” said Suzanne Noble, MD, PhD, professor of microbiology at UCSF.

These discoveries reveal potential targets for preventing C. auris from persisting on human skin. Potential therapeutic approaches include drugs that tilt the immune system away from interferon gamma signals and toward IL-17, or medications that block chitin to prevent the fungus from amplifying interferon gamma signals.

Frequently Asked Questions

What is Candida auris?

Candida auris is a multidrug-resistant pathogenic yeast capable of causing deadly outbreaks in hospitals and long-term care facilities.

How many people die from Candida auris in the U.S. each year?

According to clinical data, C. auris is responsible for roughly 3,000 deaths per year in patients in U.S. hospitals and long-term care facilities.

Where does Candida auris hide on the human body?

Researchers discovered that C. auris exhibits a strong tropism to hair follicles, taking refuge in this epidermal niche to persist on the skin.

How does the fungus evade the immune system?

C. auris remodels its exterior cell wall to expose more chitin, which triggers a type 1-skewed immune response and interferon-γ production that blocks normal skin antifungal defenses.