Nav: Home

How a deadly fungus evades the immune system

March 31, 2015

New research from the University of Toronto has scientists re-thinking how a lethal fungus grows and kills immune cells. The study hints at a new approach to therapy for Candida albicans, one of the most common causes of bloodstream infections.

Previously, scientists thought that Candida albicans spread by changing from a single, round cell to a long string of cells, or filaments. They thought this shape change allowed the fungus to move through the bloodstream and let its filaments penetrate tissues and destroy immune cells.

But the new study, published today in Nature Communications, shows that a little bit of sugar on the surface of fungal cells triggers the death of immune cells that would otherwise kill the fungus.

"It's not the shape-change per se that enables the fungus to kill the immune cell, but what happens along with it," says Professor Leah Cowen, lead researcher on the study who holds the Canada Research Chair in Microbial Genomics and Infectious Disease in U of T's Department of Molecular Genetics. "The addition of glycosylated proteins, which are proteins with a sugar attached, re-models the surface of the fungal cells."

Cowen and her lab found that Candida albicans can kill immune cells even after its cells have died. They let immune cells called macrophages consume the fungus, and after an hour they removed the fungal cells from the macrophages. Then they exposed new macrophages to fungal cells that had been consumed and those that had not, and they compared the results.

"The fungal cells that were never internalized by macrophages couldn't kill the fresh macrophages, but those that had been inside a macrophage could kill beautifully," says Cowen. That finding was a clue. The researchers reasoned that the change in the fungal cells that turned them into killers was probably on their surface, since dead cells have no active internal processes.

The researchers then used an enzyme called Endo H to snip off sugars on the glycosylated proteins attached to the dead fungal cells. The change completely blocked the ability of the fungus to kill -- a strong lead on a new and needed therapeutic strategy for Candida albicans.

Globally, fungi kill more than 1.5 million people a year. In the U.S., Candida fungi account for almost 90 per cent of hospital-acquired fungal infections, and in Canada they're the third most common cause of bloodstream infections in intensive care units. More than 40 per cent of people with a systemic Candida albicans infection will die.

A therapy that targets the ability of fungal cells to outfox the immune system would be promising, says Cowen, because it might minimize effects on healthy microbes and avoid spurring drug resistance.

As well, some anti-fungals in development -- including one in Cowen's lab -- are hindered because the target proteins are present in both fungi and humans. That means a drug has to distinguish between the fungal and human versions of the target. "If you develop a drug that targets something that's only found in fungi, it's less likely to have side effects in a human," says Cowen.

In her Nature Communications study, Cowen used a powerful Candida albicans mutant library, which the pharmaceutical company Merck recently made public. The library let Cowen and her team test the function of almost all genes in the Candida albicans genome, where before they could test just 10 per cent. "It really let us approach this pathogen from a holistic perspective and evaluate the role of all its genes in disease," says Cowen.

The researchers used the library to do the first genome-scale analysis of the fungus's ability to change shape and grow, and they discovered more than 800 regulators of this process, which they published today with their other findings.

"It's cool because we have a ton of new biology to explore, hundreds of possible drug targets and a new appreciation of how fungal pathogens interact with immune systems," says Cowen. "It's been a lot of fun."

University of Toronto

Related Immune System Articles:

Too much salt weakens the immune system
A high-salt diet is not only bad for one's blood pressure, but also for the immune system.
Parkinson's and the immune system
Mutations in the Parkin gene are a common cause of hereditary forms of Parkinson's disease.
How an immune system regulator shifts the balance of immune cells
Researchers have provided new insight on the role of cyclic AMP (cAMP) in regulating the immune response.
Immune system upgrade
Theoretically, our immune system could detect and kill cancer cells.
Using the immune system as a defence against cancer
Research published today in the British Journal of Cancer has found that a naturally occurring molecule and a component of the immune system that can successfully target and kill cancer cells, can also encourage immunity against cancer resurgence.
First impressions go a long way in the immune system
An algorithm that predicts the immune response to a pathogen could lead to early diagnosis for such diseases as tuberculosis
Filming how our immune system kill bacteria
To kill bacteria in the blood, our immune system relies on nanomachines that can open deadly holes in their targets.
Putting the break on our immune system's response
Researchers have discovered how a tiny molecule known as miR-132 acts as a 'handbrake' on our immune system -- helping us fight infection.
Decoding the human immune system
For the first time ever, researchers are comprehensively sequencing the human immune system, which is billions of times larger than the human genome.
Masterswitch discovered in body's immune system
Scientists have discovered a critical part of the body's immune system with potentially major implications for the treatment of some of the most devastating diseases affecting humans.
More Immune System News and Immune System Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Climate Mindset
In the past few months, human beings have come together to fight a global threat. This hour, TED speakers explore how our response can be the catalyst to fight another global crisis: climate change. Guests include political strategist Tom Rivett-Carnac, diplomat Christiana Figueres, climate justice activist Xiye Bastida, and writer, illustrator, and artist Oliver Jeffers.
Now Playing: Science for the People

#562 Superbug to Bedside
By now we're all good and scared about antibiotic resistance, one of the many things coming to get us all. But there's good news, sort of. News antibiotics are coming out! How do they get tested? What does that kind of a trial look like and how does it happen? Host Bethany Brookeshire talks with Matt McCarthy, author of "Superbugs: The Race to Stop an Epidemic", about the ins and outs of testing a new antibiotic in the hospital.
Now Playing: Radiolab

Speedy Beet
There are few musical moments more well-worn than the first four notes of Beethoven's Fifth Symphony. But in this short, we find out that Beethoven might have made a last-ditch effort to keep his music from ever feeling familiar, to keep pushing his listeners to a kind of psychological limit. Big thanks to our Brooklyn Philharmonic musicians: Deborah Buck and Suzy Perelman on violin, Arash Amini on cello, and Ah Ling Neu on viola. And check out The First Four Notes, Matthew Guerrieri's book on Beethoven's Fifth. Support Radiolab today at