Candidalysin: a newly discovered fungal toxin

My project focuses on one of the most common fungal species Candida which affects around 85 million people each year. We have recently discovered a new toxin found to be produced by this fungus called Candidalysin.

Interestingly Candidalysin is only produced when the fungus is in its active form when it's able to infect and penetrate deep into tissues.

We've also shown that Candidalysin is also directly responsible for the cell damage and inflammation observed during infection although the mechanisms are currently unknown.

Our aim therefore is to identify interactions between Candidalysin and the human host to understand how this toxin is able to exert its effects. This will inform as to how we might manipulate these effects leading to the generation of a protective antifungal responses.

Identification of such interactions could significantly enhance anti-candida treatments particularly in at risk patient groups where infections can be fatal.

Dr Jemima Ho works in Dr Julian Naglik's lab at King's College London.

Dealing with diversity – immune responses to fungi

Fungi are everywhere. They’re present in the air, in our food, some even live inside our bodies. But most of us rarely think about diseases caused by fungi. This is because our defences do a really good job in keeping them in check.

However for millions of people whose immune system are defective fungi can cause serious infections that are hard to treat and can be life threatening.

A group of cells called phagocytes play a key role in keeping us safe from fungi. They normally patrol our body so when there’s a breach they are the first to respond. Their function is to seek eat and destroy microbial intruders.

But no all fungi are alike. My Ph.D. project aims to understand how phagocytes tackle such different targets. So far I have found there are huge differences in the rate at which various different fungi are engulfed by phagocytes.

The speed of these processes depends on the chemical composition of the fungi, whether they are alive or dead, and whether they are coated with human proteins that help to mark them as intruders.

Understanding the basic biology behind these processes is the first step towards developing new treatment strategies.

Maria Fernanda Alonso works in Professor Neil Gow's lab at the University of Aberdeen.

The role of mitochondria in fungal pathogenesis

Candida albicans is one of the fungal species most commonly causing life threatening infections in vulnerable patients. Our group is studying the mitochondria in Candida albicans cells.

Just like in our cells the mitochondria are the batteries of the cell, producing energy required for growth and in fungal cells can also influence infection.

The mitochondria can influence components of the fungal cell wall and its ability to infect us.

If we understand how mitochondria are influencing these factors, we can develop new anti-fungals or we can use existing anti-fungals in new combinations in order to tackle life threatening infections.

Lucian Duvenage works in Dr Campbell Gourlay's lab at the University of Kent

Human lung cells: a defence against fungal spores

Every day we inhale hundreds of fungal spores but these in healthy individuals are efficiently eliminated by specialist immune cells called phagocytes which engulf and kill them. However, some human illnesses interfere with this defence mechanism, increasing susceptibility to fungal diseases.

A specialist lung tissue called the epithelium is the first line of contact between the inhaled spores and us, the host. We are working to understand how the lung epithelium interacts with the spores of a common mould called Aspergillus fumigatus.

We have generated fluorescent Aspergillus and combined this with fungal and host specific dyes to directly visulaise this interaction. We have discovered that epithelial cells ingest fungal spores and kill them.

This might provide a critical defence mechanism which is acting while we breathe, and before even phagocytes arrive at the site of the infection.

We are now trying to work out how epithelial cells grab and ingest fungal spores, by using fluorescent fungal mutants and targeted elimination of host proteins.

Once we understand this process in detail we can design new therapies to assist a quicker elimination of the dangerous fungal spores we all inhale on a daily basis.

Dr Margherita Bertuzzi works in Dr Elaine Bignell's lab at the University of Manchester

The heat is on; cooling down the response to Aspergillus

My research is focused on infections caused by Aspergillus, which is present in the environment all around us. We each inhale hundreds of fungal spores every single day, and for the majority of people this doesn't cause any problems, but for people whose immune system isn't working properly Aspergillus can cause serious, even life threatening, infections.

One group of patients who are at particular risk of Aspergillus infection are people with a rare inherited immune deficiency called chronic granulomatous disease, or CGD.

For these patients infection with Aspergillus is frequently fatal, even with appropriate anti-fungal treatment.

My research so far suggests that rather than not mounting a sufficient immune response, the CGD immune system actually over-reacts to Aspergillus, causing significant tissue damage but without clearing the fungal infection.

We're therefore looking at whether we can use new treatments aimed at reducing inflammation alongside conventional anti-fungal drugs to improve the outcome of these devastating infections for CGD patients.

Dr Jill King works in Professor Adilia Warris's lab at the University of Aberdeen

Our microscopic army against fungal killers

Cryptococcus, like many fungi, produces spores that are found in the air that we breathe. These spores will be inhaled into our lungs but they do not cause any harm because of our immune defences. However, they can cause life-threatening infections in individuals that have a weakened immune system, for example those that have AIDS or have had an organ transplant.

So, we're interested in immune cells called macrophages which are needed for immune defence against Cryptococcus.

It is impossible to see how immune cells destroy this fungus during infection because we do not have see-through bodies. So, in order to study this we are using zebrafish. Zebrafish have a similar immune system like our own but are transparent which makes it possible to see how infections happen. Using zebrafish we are testing new ways to enhance immune defences against Cryptococcus.

Ultimately these investigations may lead to development of novel therapies towards Cryptococcal infections.

Alfred Kamuyango works in Professor Simon Johnston's lab at the University of Sheffield.

How yeasts survive stress in the human body

My research focuses on the pathogenic yeast Candida glabrata which causes often fatal systemic blood stream infections in humans. In particular, I'm investigating how Candida glabrata survives stresses in the human environment. For example, when our blood cells encounter invading microorganisms in our blood certain immune cells will engulf the invading microorganisms and release toxic chemicals to kill them.

However, Candida glabrata is able to survive this and will replicate inside blood cells and go on to cause disease. To further understand how Candida glabrata survives stresses encountered in the human environment

I have designed a number of mutants which we have examined. We found that some mutants were able to survive stresses better than others and when we examine the DNA of the stress resistant mutants, we were then able to identify genes that are important for infection.

Once we've identified genes which are important for causing disease we can then go on to research these further and use them as potential targets for developing novel therapeutics to treat fungal disease.

Dr Lauren Ames works in Professor Ken Haynes's lab at the University of Exeter.

The host-pathogen struggle for nutrients

We can view an infection as a battle between the human host and the microbial invader. The outcome of which decides whether the host remains healthy or succumbs to disease. As this battle rages microbial invaders use their hosts as a source of nutrients.

However, the human body has evolved complex systems to limit access to certain essential nutrients in an attempt to starve the invading microbes and prevent disease.

We call these processes nutritional immunity. Therefore, to win the battle and cause disease microbial pathogens must have evolved strategies to thrive in a nutritionally restrictive environment within its infected host.

We are interested in exploring how the human fungal pathogen Candida albicans adapts to limitations to essential trace nutrient zinc. We have identified specific coping mechanisms that are adopted by this fungus in order to deal with nutritional immunity. In response to zinc starvation, Candida albicans dramatically changed their cell shape.

We therefore want to know how this change is regulated and what impact it has on the progression of infection with the ultimate aim to therapeutically manipulate the system and push the balance back in favour of the human host to prevent disease.

Dhara Malavia works in Dr Duncan Wilson's lab at the University of Aberdeen.