Efficient assassin – insights into how C. auris disables and evades the immune system

Candida auris (in blue) uses immune cells as a niche within which to proliferate during infection.
Candida auris (in blue) uses immune cells as a niche within which to proliferate during infection.

Fungal pathogens have a major global impact on human health as they become more common and increasingly resistant to treatment - and last year the World Health Organization published the first-ever list of fungal "priority pathogens" – a catalogue of fungi representing the greatest threat to public health. Despite not being known as a pathogen until 2009, Candida auris (C. auris) is one of four of the WHO’s “critical priority” pathogens on that list and its prevalence is increasing. In 2016 a C. auris infection closed down an Intensive Care Unit in the UK after three deaths, and C. auris was transmitted between patients, something that is rarely seen in fungal infection.

Now, in a paper published in the journal Cell Reports, scientists from the Monash Biomedicine Discovery Institute have revealed the strategies that C. auris uses to evade the body’s immune system. The silent assassin was caught on video surveillance, attacking immune cells over 24 hour periods in both mouse and human samples.

The research, led by Dr Harshini Weerasinghe and Professor Ana Traven, in the only laboratory in Australia studying this deadly pathogen in depth, has shown that C. auris infects and kills macrophages, an important human immune cell that would normally eat, contain and kill invading pathogens. Moreover, C. auris is also able to avoid being recognised as a threat by these immune cells, which means that the immune response normally activated when microbial pathogens are recognised, isn’t active in response to C. auris.

According to Professor Traven, C. auris is a sophisticated killing machine. “This pathogen not only escapes and kills the immune cells that would normally be a threat, but it also somehow hides from being recognised as danger despite this killing so that other immune cells don’t target it as well,” she said.

The importance of the research is that scientists and pharmaceutical companies have an insight into the way C. auris operates, opening the way to develop therapeutic targets for C. auris infections. To date C. auris infections, which target the bloodstream and have a high associated mortality, are difficult to treat.

C. auris is considered by the WHO to be such a serious global health threat because it is resistant to almost all antifungal drugs currently in use. Usually, patients also have their immune system to protect them from infection. We now show a mechanism by which C. auris can escape immune responses, which means that it is not only resistant to antifungal therapeutics but also has ways to survive immune responses,” Dr Weerasinghe said.

Using infection models, the research also reveals that the strategies used by C. auris to evade the immune system allow it to grow in infection niches, such as in the kidney. These strategies involve the ability of C. auris to deplete nutrients that the immune cells need to survive.

As such, Professor Traven said the insights provided by the research provide possible ways forward for therapeutic innovation. “Now that we know more about the nutrients and metabolic pathways that C. auris and immune cells need while they fight against each other, we can start thinking about how we could intervene in these immune-evading strategies that C. auris has developed.”

Read the full paper, published in Cell Reports, titled Candida auris uses metabolic strategies to escape and kill macrophages while avoiding robust activation of the NLRP3 inflammasome response

DOI - 10.1016/j.celrep.2023.112522

E: taniaewing@taniaewing.com
M: +61 (0) 408 681 293

Monash Media
E: media@monash.edu
T: +61 (0) 3 9903 4840

About the Monash Biomedicine Discovery Institute
Committed to making the discoveries that will relieve the future burden of disease, the Monash Biomedicine Discovery Institute (BDI) at Monash University brings together more than 120 internationally-renowned research teams. Spanning seven discovery programs across Cancer, Cardiovascular Disease, Development and Stem Cells, Infection, Immunity, Metabolism, Diabetes and Obesity, and Neuroscience, Monash BDI is one of the largest biomedical research institutes in Australia. Our researchers are supported by world-class technology and infrastructure, and partner with industry, clinicians and researchers internationally to enhance lives through discovery