Plasma membrane lipids and their role in fungal virulence

Abstract

There has been considerable evidence in recent years suggesting that plasma membrane lipids are important regulators of fungal pathogenicity. Various glycolipids have been shown to impart virulent properties in several fungal species, while others have been shown to play a role in host defense. In addition to their role as virulence factors, lipids also contribute to other virulence mechanisms such as drug resistance, biofilm formation, and release of extracellular vesicles. In addition, lipids also affect the mechanical properties of the plasma membrane through the formation of packed microdomains composed mainly of sphingolipids and sterols. Changes in the composition of lipid microdomains has been shown to disrupt the localization of virulence factors and affect fungal pathogenicity. This review gathers evidence on the various roles of plasma membrane lipids in fungal virulence and how lipids might contribute to the different processes that occur during infection and treatment. Insight into the role of lipids in fungal virulence can lead to an improved understanding of the process of fungal pathogenesis and the development of new lipid-mediated therapeutic strategies.

The putative flippase Apt1 is required for intracellular membrane architecture and biosynthesis of polysaccharide and lipids in Cryptococcus neoformans

“…Therefore, we asked whether other key lipids would be affected by APT1 deletion. To address this question, molecules related to the synthesis of glucosylceramide (GlcCer), inositolphosphoryl ceramides (IPCs) and sterylglycoside were chosen, since these three lipid classes are linked to cellular physiology and/or immunopathogenesis of cryptococcal infection [15,46–48]. Lipid extracts of WT, mutant and complemented cells were analyzed after cultivation of fungal cells for 48 or 72 h. Among the 60 lipids included in our analysis, some major lipid classes were changed in the flippase mutant exclusively after 48 h of cultivation.…”

“…These pathogens produce a range of virulence factors that regulate survival in the host (reviewed in [5]). Cryptococcal virulence factors include extracellular enzymes (laccase, urease and phospholipase Bl), lipids and the secreted polysaccharide glucuronoxylomannan (GXM), a major capsular component [6–15]. GXM is thought to be constitutively secreted into fungal cultures and host tissues [12,16].…”

Changes in glucosylceramide structure affect virulence and membrane biophysical properties of Cryptococcus neoformans

“…GlcCer accumulation and morphological changes in red blood cells have been suggested to hamper cell deformability, which prevents the circulation of red blood cells in capillaries (48). The structure of the GlcCer accumulated in the Δ sld8 strain is identical to the saturated, mammalian GlcCer, which accumulates in red blood cells in Gaucher disease (49). It is likely that the accumulation of a “mammalian” GlcCer on fungal membrane leads to a rigid membrane, which cannot sufficiently deform to travel through the capillaries and enter brain microvasculature, thereby preventing the establishment of a virulent and invasive cryptococcosis.…”

Antifungal activities of the essential oil and its fractions rich in sesquiterpenes from leaves of Casearia sylvestris Sw.

“…Hence, molecules that cause conformational changes in the integrity of fungal membranes may help in rational drug design (Cannon et al 2009, Rella et al 2016.…”