I’m guessing you’ve all heard of oral or genital thrush. It’s very common- one-third of women will have an incidence of vaginal thrush once in their lifetime. You may think thrush is a nasty infection, however the fungus that causes it (Candida albicans) can also enter the bloodstream and spread throughout the body to cause invasive candidiasis, which is much worse.
Symptoms for invasive candidiasis are non-specific, generally they include fever and chills and other symptoms that vary depending on the site of infection. If I haven’t convinced you that it’s bad yet, due to these non-specific symptoms detection and diagnosis generally occurs late in the disease, resulting in a death rate as high as 40%!
Don’t worry, Candida is an opportunistic pathogen, meaning that it’s generally not until the immune system is impaired that invasive candidiasis will occur. One such example of immune system impairement is in individuals with HIV/AIDS- With this growing pandemic there has been an increased incidence of invasive candidiasis. As it’s currently the leading fatal fungus and a continually growing problem, there has been research to find out the exact mechanism of invasion. A paper entitled “Hsp90 Orchestrates Temperature-Dependent Candida albicans Morphogenesis via Ras1-PKA Signaling” is one of many that try to unravel some of this mystery.
Why is C. albicans so Virulent?
C. albicans can exist in (and switch between) different morphologies: the main two being budding and filamentous yeast. This morphogenesis is important in the virulence of this fungus, as C. albicans deficient in filamentous formation have defective invasion properties. This means that if you prevent the filamentous formation of C. albicans you can stop or prevent the infection. Great! Now we know how to stop them, but why haven’t we done so already? Well, unfortunately it isn’t that easy. Before we can prevent this change in morphology we must understand the mechanisms which cause it.
What Causes Morphogenesis?
It has already been shown that C. albicans morphogenesis is caused by environmental factors including nutrient limitation, pH, CO2, serum and temperature. However, there are gaps in the knowledge of the exact mechanisms that link these factors with filamentous formation. The previously mentioned paper tries to explain why a change from 30°C to 37°C causes a change from budding to filamentous yeast by linking temperature to Hsp90.
Hsp90 and the Ras-PKA pathway
Hsp90 is a molecular chaperone, meaning that it aids the folding/unfolding and assembly/disassembly of other molecules. The theory behind this paper is that if temperature increases then there’s increased unfolding of proteins. In this case, with specific reference to Hsp90, a rise in temperature results in compromised Hsp90 which in turn results in filamentous formation. They therefore hypothesise that filamentation should still occur if Hsp90 is compromised without temperature increasing. This hypothesis was subsequently supported, meaning that Hsp90 is an inhibitor of filamentation. Furthermore, they showed the link between Hsp90 and the Ras-PKA signalling pathway. By showing Hsp90 does not repress this pathway via stabilizing negative regulators, it can also be assumed that Hsp90 acts to repress positive regulators of the pathway.
As Tomas Hobbes wrote, “knowledge is power”. Hopefully the increased understanding of C. albicans and the exact mechanisms of its virulence will aid prevention, treatment and cure development. There is also the hope that knowledge of this yeast can help to explain temperature dependant properties and metamorphic properties of other pathogens.
The possibilities are endless…
Shapiro RS, Uppuluri P, Zaas AK, Collins C, Senn H, Perfect JR, Heitman J, & Cowen LE (2009). Hsp90 orchestrates temperature-dependent Candida albicans morphogenesis via Ras1-PKA signaling. Current biology : CB, 19 (8), 621-9 PMID: 19327993