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Understanding the enemy
Most fungi live as unseen microscopic spores and filaments in the environment around us, and some even live in our guts and on our skin as part of our normal flora. In most cases, fungi do us no harm and it is only when our immune system falters, for example through immunosuppressive treatments or HIV-AIDS immunodeficiency, that fungi gain the upper hand.
Unlike viruses and bacteria, fungal cells are very similar to our own, but with a few key differences. By identifying and studying these, we can find out whether they can be exploited to help combat disease. For example, fungal cells are surrounded by a stiff cell wall. Detecting this helps us to diagnose infections and it is an effective drug target because it is essential for survival of the fungus.
Unlike viruses and bacteria, fungal cells are eukaryotes and very similar to our own, but with a few key differences. By identifying and studying these, we can find out whether they can be exploited to help combat disease. For example, fungal cells are surrounded by a stiff cell wall. Detecting this helps us to diagnose infections and it is an effective drug target because it is essential for survival of the fungus.
Click on the red circles below to learn more about the structure of the fungal yeast cell.
Vacuoles are enclosed compartments that function as the storehouse of the cell. They contain inorganic and organic molecules, such as trace metals and soluble enzymes that are released when needed for cell-signalling or re-building. Sometimes they contain molecules that have entered the cell by diffusion or engulfment but are of no use to the cell. The vacuole can store these molecules so they cause no harm.
A bud scar is a ring of very tough cell wall material that is left behind after a new daughter cell has separated from the mother cell. It is made of a cell wall component called ‘chitin’, which is the same sugar polymer that is found in the shells of crabs and molluscs and is one of the strongest biopolymers known.
It protects the cell from the outside environment but contains tightly-controlled channels, transporters and signalling molecules so that the cell can take up nutrients and communicate with other cells. In mammals, the fluidity of the cell membrane is influenced by the small molecule, cholesterol. Fungi make their own version of this molecule called ‘ergosterol’. Because it is fungus-specific, it is the target of the important antifungal drug, fluconazole.
The Golgi is part of the endomembrane system in the cytoplasm. Proteins that are destined for the cell-surface are modified in the Golgi by the addition of a variety of carbohydrate chains. The proteins are then packaged into membrane-bound vesicles, which bud off from the Golgi and are transported to the cell surface. The Golgi is therefore important for producing the layer of surface carbohydrates that form the primary point of contact with human cells.
The cell wall is a structural layer of carbohydrate fibrils that interlink to form a resilient layer outside the cell membrane. While animal cells do not form cell walls, for plants, bacteria and fungi, walls confer cell shape and are important for protection. Cell walls have to be tough, but they also have to be porous to allow the transport of nutrients. Cell walls seem rigid but they are constantly modified by the cell to allow for new growth or for additional strength when necessary. A new class of antifungal drugs called ‘echinochandins’ specifically inhibit fungal cell wall biosynthesis but do not harm human cells. You can learn more about the importance of the fungal cell wall by visiting The Fungal Surface page.
Bounded by the cell-membrane, the cytoplasm is the aqueous environment within a cell that contains all the molecules required for growth, such as sugars, salts and proteins. It surrounds and nurtures the many membrane-bound structures, called organelles, which are vital for cell division and function. These organelles include the nucleus, mitochondria and Golgi apparatus and are distributed throughout the cytoplasm in a spatially-controlled manner.
These granules are the parts of the cell that store the cell's energy reserves as well as other important metabolites.
Mitochondria are small membrane-bound organelles that generate most of the cell's supply of chemical energy in the form of adenosine triphosphate (ATP). They are often referred to as the powerhouse of the cell, although they perform many additional tasks. Mitochondria derive from an ancient bacterial life-form that was absorbed into eukaryotic cells millions of years ago and have since adapted and evolved to become the cell’s primary provider of energy.
In biology, ’septum’ (plural septa) is a Latin word for something that encloses. In fungi, the septa are internal walls that divide one cell compartment from another. In some fungi, septa contain a small opening (called a pore) so that cytoplasm and nuclei can stream from one compartment to another. In other fungi, septa are completely sealed so that each compartment exists as an isolated and individual cell.
The endoplasmic reticulum (ER) is the organelle in which the process of protein transport to the cell surface begins. Usually found near the nucleus, the ER is a tubular structure that receives new proteins as they are made, ensuring they fold correctly before being passed on to the Golgi apparatus for further modification in the onward journey to the cell surface. The endoplasmic reticulum is not found in red blood cells, or spermatozoa.
Lipid droplets, also referred to as lipid bodies, oil bodies or adiposomes, are lipid-rich cellular organelles that regulate the storage and hydrolysis of neutral lipids. Lipids are an important source of energy for the cell.
The nucleus of the cell is a rounded organelle that contains and protects genetic material. In eukaryotes, nuclei store genetic material in the form of chromosomes, which are long strands of DNA surrounded by 'nucleoplasm', the nuclear version of 'cytoplasm'. Although most of the cell’s genetic material is stored within the nucleus, a very small amount is retained by mitochondria through their evolutionarily ancient function as bacteria.
Most fungi spend part of their life-cycle growing at the tip. To do this, they need to continuously expand by adding more membrane at the growth site. New membrane lipids are delivered to the tip in the form a coating on small, round vesicles that pinch off from the Golgi. On reaching the cell tip, the lipid coating is incorporated into the membrane and the vesicle cargo of proteins and carbohydrates is released for attachment to the expanding cell wall.
The septin ring forms at the mother cell surface to mark the site where the new daughter cell will emerge. When the daughter cell is big enough, the ring splits in two so that a new wall can be built between them. Finally, the cells separate and the rings dismantle, leaving behind a bud scar on both mother and daughter cells.
Only fungi that can adapt to living in the human body cause infections. Some do this by switching to a new growth form, such as invasive filaments or giant cells, which help fungi to colonise tissue and escape immune cell attack. Others produce toxins and other molecules that help the fungus find nutrients needed for survival inside the human body.
The recent development of lab-on-a-chip techniques offers new ways to study these changes. The chips contain tiny chambers that mimic the environment of the human host. Using them, we can investigate how fungi adapt and the effect of new antifungal drugs. We can also monitor how fungi interact with host immune cells in real time.
By increasing our understanding of the biology of fungi, we are finding better ways to diagnose and treat disease, thereby improving the outcome for patients in the battle for survival between pathogen and host.
Credits
Alexandra Brand (text and interactive cell guidance) Jude Bain (left and background image) Tina Bedekovic (right image)
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