Abstract
The phospholipids phosphatidylserine (PS) and phosphatidylethanolamine (PE) play important roles in the virulence of Candida albicans and loss of PS synthesis or synthesis of PE from PS (PS decarboxylase) severely compromises virulence in C. albicans in a mouse model of systemic candidiasis. This review discusses synthesis of PE and PS in C. albicans and mechanisms by which these lipids impact virulence in this fungus. This is further compared to how PS and PE synthesis impact virulence in other fungi, parasites and bacteria. Furthermore, the impact of PS asymmetry on virulence and extracellular vesicle formation in several microbes is reviewed. Finally, the potential for PS and PE synthases as drug targets in these various kingdoms is also examined.
Highlights
Understanding the roles for lipids in the virulence of microbial pathogens has long been an area of interest
In addition to an internal, membrane-bound PS decarboxylase, it has a second, soluble PS decarboxylase enzyme (TgPSD1) that is secreted extracellularly from T. gondii cells and appears to decarboxylate PS to PE in the parasitophorous vacuole, an organelle within the host where T. gondii reproduces [57]. This is unusual because both PS decarboxylase and PS synthase are typically membrane bound enzymes with multiple transmembrane domains, there have been other reports of hyper-expressed PS decarboxylase enzymes dissociating from the cytoplasmic membrane in bacteria [58] and in Plasmodium falciparum [59,60]
The mechanisms responsible for cell wall unmasking in the cho1∆∆ mutant are currently under investigation. These defects in virulence in the cho1∆∆ and psd1∆∆ psd2∆∆ mutants are manifest despite the presence of an alternative Kennedy pathway for PE synthesis (Figure 2)
Summary
Understanding the roles for lipids in the virulence of microbial pathogens has long been an area of interest. Within the broad category of lipids are many different subtypes, including sphingolipids, phospholipids and sterols Most of these have been implicated in virulence across a wide range of pathogens [11,18,19,20,21,22]. A number of more recent reports reveal interesting roles for PS and PE in the virulence of Candida albicans as well as a variety of protozoan and prokaryotic pathogens. A number of more reveal interesting roles for PS andtheir in theinvirulence ofHowever, Candida albicans as well as a recent varietyreports of protozoan and prokaryotic for PS and PE in communication the virulence of will. Candida albicans asPS well a variety of and protozoan and the prokaryotic pathogens. We will compare this to what has been learned in other pathogens and a in few other eukaryotic pathogensIsand a few prokaryotes
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