The New Fungus Among Us, Candida auris

In “The Last of Us,” a video game and recently-wrapped HBO series, giant mutant fungi turn much of humanity into zombies. In real life, another fungus, the yeast Candida auris, is spreading, just as COVID finally fades.

Candida auris is the first multi-drug resistant fungus identified. It is deadlier than familiar relative Candida albicans, which lies behind common vaginal and throat infections. Candida yeasts are normal inhabitants of our skin and other superficial body parts, but are dangerous when they enter the bloodstream or reach solid organs, like the heart or kidneys.

“What is different and particularly scary about Candida auris is that it can survive on skin and healthcare surfaces up to two weeks, allowing the spread from person-to-person in healthcare settings and nursing homes. This fungus is not usually killed by clinically used antifungal drugs, which makes infection difficult to treat and can often result in death. It is also difficult to identify with standard laboratory methods,” summed up Mahmoud Ghannoum, director of the Center for Medical Mycology at University Hospitals Cleveland Medical Center.

CDC and other public health organizations are deploying whole genome sequencing to track the spread of this fungus around the world. The agency launched FungiNet in 2021, as “a network for molecular surveillance and genomic epidemiology for fungal diseases,” with initial focus on C. auris. The online resource “supports nationwide laboratory capacity to rapidly detect, prevent, and respond to drug resistance” to the infection.

Comparing whole genome sequences can reveal where the pathogen is coming from and where it is likely going – surveillance notoriously delayed in the US, compared to other nations, when COVID hit.

Toilet Tracking of COVID

For three years, the wall facing the toilet in my bathroom has been festooned with the latest color-coded map of the lineages of SARS-CoV-2, the COVID coronavirus. One can ponder viral evolution while on the porcelain throne.

Early versions of my bathroom chart followed public health agencies in depicting the nations where COVID was initially identified. After this was deemed stigmatizing, I tracked the Greek letter identifiers, traipsing from alpha to beta to delta to gamma with a few oddballs like zeta, until evolution stalled and then burst into a flurry of tinier branches once Omicron came along. The newbie viral variant branched once, then one of those initial branches diverged again, yielding BA.1 which begat BA1.1 as well as BA.2, which split into five branches that in turn became ten others. I stopped updating once that happened.

The first genome sequence of SARS-CoV-2 was posted to the world astonishingly fast, on January 11, 2020. Things then ramped up quickly, mostly from outside the US, and I would often peruse The GISAID Initiative website for the numbers of viral genomes sequenced. Tick, tick, boom! It currently tops 15 million.

GISAID began in 2006 in response to bird flu, becoming a global clearinghouse for data and maps galore on epidemic and pandemic viruses. For those who claim nothing’s being done to prevent future pandemics, please look at GISAID.

Comparing genome sequences is important because they provide a 4-letter language in the bases A, C, G, and T (for DNA) or A, C, G, and U (for RNA). The sequences are used to trace evolution based on a single assumption: the more alike two species or strains or even individuals are in their nucleic acid sequences, the more recently they shared an ancestor. And so these data are used to deduce evolutionary trees – sometimes more than one can account for the clues in the language of genetics.

The viral lineages on my bathroom wall are no different in concept than the evolutionary tree in my human genetics textbook that depicts Homo sapiens sapiens diverging from Neanderthals and Denisovans, which diverged from other members of Homo farther back, and australopithecines farther still. The lineages comprising evolutionary trees, from people to viruses, are called phylogenies. It’s an old technique.

Tracking the New Pathogen

The initial clinical identification of Candida auris was in Japan in 2009, but stored cultures reveal that it goes back to at least 1996, in South Korea. CDC calls it an “emerging pathogen” because it has since shown up in more than 30 nations. The agency started tracking it in 2013, and the spread accelerated in 2015.

A 2018 report from CDC’s US Candida auris Investigation Team, published in Lancet Infectious Diseases, compared whole genome sequences of the yeast from patients in ten US states and from India, Colombia, Japan, Pakistan, South Africa, South Korea, and Venezuela.

The study focused on single-base places in the genome that can vary (single nucleotide polymorphisms, aka SNPs), from country to country, patient to patient, and even within an individual. The team also considered travel history and contacts that could have fostered spread. The US cases “were genetically related to those from four global regions, suggesting that C. auris was introduced into the USA several times. Genetic diversity among isolates from the same patients, health-care facilities, and states indicates that there is local and ongoing transmission,” the report concluded.

So it’s here.

In 2022, CDC reported 2,377 cases from patients and another 5,754 from their contacts, mostly from California, Nevada, Texas, New York, Florida, and Illinois. But that may be an undercount if some clinicians are not yet reporting (or perhaps recognizing) cases.

Who’s at Risk?

C. auris, like many pathogens, is particularly dangerous to patients in hospitals, where it enters the bloodstream and spreads, within the individual and to others. It also infects ears (hence the “auris”) and wounds, and possibly also the lungs and bladder because yeast are found in sputum and urine.

At highest risk are patients with tubes piercing body parts or who’ve extensively used certain broad spectrum antifungals or antibiotics. Mortality rate approaches 60%, but many patients are already very sick if they’re infected while hospitalized for something else.

The yeast spreads through the air and from contact with contaminated fungus-bearing surfaces. And people of any age can be infected.

Identifying C. auris requires special lab tests and tools to culture the yeast; it is easily confused with other Candida species. And it resists many conventional anti-fungals. The most effective drugs are the echinocandins, but combinations of drugs may be necessary to control the infection.

The search is on for new antifungals. Case Western Reserve University, for example, has just received a $3 million grant from the NIH to develop novel treatments.

But I suspect much research is still in the preclinical (mice and molecules) stage because Clinicaltrials.gov lists only three projects for the yeast, from India, Pakistan, and South Africa. A vaccine being developed at the Lundquist Institute of UCLA so far works in mice and can be teamed with antifungals.

Meanwhile, whole genome comparisons continue to inform, trace, and possibly even predict where the yeast has spread and perhaps get ahead of it to prevent outbreaks. By considering genome data along with other information, investigators can identify how people became exposed, where the fungi are likely to move geographically, and even reveal introductions of the pathogen into new areas before outbreaks occur or are detected.

Imagine if we could have done that with COVID!