Candida albicans: Mechanisms of biofilm resistance unraveled?

Candida albicans is currently the fourth most common bloodstream infection in the world. It is the most widespread fungal pathogen and is associated with a wide range of clinical symptoms. C. albicans can grow in a variety of distinct morphological forms, ranging from unicellular budding yeast to hyphae. This fungus can be found as a free floating planktonic C. albicans or as a biofilm, as happens in disease states. Candidiasis is associated with biofilm formation on a wide range of implanted medical devices. Our immune system is not capable to defeat a C. albicans biofilm, therefore removal of the medical device is necessary. Knowing this, it is interesting to understand through which mechanisms a C. albicans biofilm is more resistant than its planktonic form. C. albicans biofilms are made of yeast, a large amount of hyphae and an extracellular matrix. The cell wall of C. albicans consists of a skeletal component containing β-glucans and chitin, and a matrix component consisting out of glycosylated proteins with mannan and carbodhydrates. These can be recognized through opsonisation by antibodies, complement and Mannose binding protein. But also directly by pattern recognition receptors of mononuclear phagocytic cells. These consist out of Toll-like receptors, mannose receptors which recognize mannan, CR3 and dectin-1 receptors that recognize β-glucans. After recognition C. albicans can be phagocytised, where the dectin-1 receptor plays an important role. Inside the phagolysosome, the fungus can be killed by oxygen-dependant pathways like superoxide anion and hydrogen peroxide mediated killing and non-oxygen dependant pathways. Most likely C. albicans will go into apoptosis after oxidative stress. But C. albicans is capable of resisting the different steps described above. It can cover the β-glucans in hyphae by mannans and α-glucans, thereby preventing detection by dectin-1. Other mechanisms are the inhibition of oxygen radicals by enzymes like catalase and even preventing the release of an oxidative burst by mononuclear cells. In biofilms it is even more specific, as they are less susceptible to these reactive oxygen species. But the immune system also helps C. albicans through these mononuclear cells as they raise the ability of C. albicans to form a hypha-rich biofilm. One of the ways is through the release of specific cytokines. But C. albicans also produces a metabolic product, farnesol, which prevents the formation of biofilms and upregulates the epithelial cell defense. In conclusion, there are three very important players in the resistance of C. albicans to our immune system. First of all, the extracellular matrix, which makes it more difficult for immune cells to infiltrate the biofilm. It also makes the C. albicans biofilm less susceptible to molecules released by the mononuclear immune cells. Secondly, biofilms contain a lot of hyphae, dectin-1 recognition is prevented and therefore phagocytosis does rarely occur. The last way, is the ability of C. albicans to recruit mononuclear immune cells to build a hyphae-rich biofilm. In order to defeat C. albicans, these resistance factors have to be minimized. Thereby giving the advance in our body, back to the immune system.