Abstract
We previously reported that 3-hydroxy fatty acids promoted the survival of cryptococcal cells when acted upon by amoebae. To expand on this, the current study sought to explain how these molecules may protect cells. Our data suggest that 3-hydroxy fatty acids may subvert the internalization of cryptococcal cells via suppression of the levels of a fetuin A-like amoebal protein, which may be important for enhancing phagocytosis. Additionally, we show that an acapsular strain (that is devoid of 3-hydroxy fatty acids) was protected against the effects of hydrogen peroxide when exogenous 3-hydroxy fatty acids were present, but not in the absence of 3-hydroxy fatty acids. A similar response profile was noted when a strain with a capsule was challenged with hydrogen peroxide. We also show that cryptococcal cells that naturally produce 3-hydroxy fatty acids were more resistant to the effects of amoebapore (an amoeba-specific hydrolytic enzyme), compared to cells that do not produce these molecules. Taken together, our findings suggest that 3-hydroxy fatty acids possess an anti-phagocytic activity that may be expressed when cells interact with macrophages. This may allow the yeast cells to evade immuno-processing.
Highlights
3-Hydroxy fatty acids are lipid-based molecules that are oxygenated and whose amphiphilic quality is evident when immersed in water (Tsitsigiannis and Keller, 2007; Sebolai et al, 2012)
Our results suggest that amoebae produce a fetuin A-like protein (Figure 1), which may have a similar function as that expressed in macrophages
To test the effectiveness of amoebapore in killing cryptococcal cells, we considered its activity against four strains: (1) one that has a capsule and produces 3-hydroxy C9:0 (UOFS Y-1378), (2) two that have capsules but no 3-hydroxy C9:0 (R265 and LMPE 046), and (3) one without a capsule and 3-hydroxy C9:0 (LMPE 101) (Figure 4)
Summary
3-Hydroxy fatty acids are lipid-based molecules that are oxygenated and whose amphiphilic quality is evident when immersed in water (Tsitsigiannis and Keller, 2007; Sebolai et al, 2012). 3-hydroxy fatty acids are intermediate products that are poorly catalyzed by 3-hydroxyacyl-CoA dehydrogenase and are secreted (Sebolai et al, 2008) This escape from the mitochondria suggests these molecules have no apparent function in the primary catabolism of the concerned organism. In an attempt to elucidate the function(s) of these molecules, Madu et al (2015) studied how they may influence Cryptococcus-amoeba interactions These researchers concluded that, at a physiological concentration, 3-hydroxy fatty acids protected cryptococcal cells by impairing the ability of amoeba to internalize and phagocytose cells. This study may offer insight into how these molecules could assist cells to evade immuno-processing when acted upon by macrophages, which are said to have evolved from free-living amoebae (Siddiqui and Khan, 2012)
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