Trapping toxins within lipid droplets is a resistance mechanism in fungi

Abstract

Lipid droplets (LDs) act as intracellular storage organelles in most types of cells and are principally involved in energy homeostasis and lipid metabolism. However, the role of LDs in resistance to toxins in fungi remains largely unknown. Here, we show that the trapping of endogenous toxins by LDs is a self-resistance mechanism in the toxin producer, while absorbing external lipophilic toxins is a resistance mechanism in the toxin recipient that acts to quench the production of reactive oxygen species. We found that an endolichenic fungus that generates phototoxic perylenequinones (PQs) trapped the PQs inside LDs. Using a model that incorporates the fungicidal action of hypocrellin A (HA), a PQ derivative, we showed that yeast cells escaped killing by trapping toxins inside LDs. Furthermore, LD-deficient mutants were hypersusceptible to HA-mediated phototoxins and other fungicides. Our study identified a previously unrecognised function of LDs in fungi that has implications for our understanding of environmental adaptation strategies for fungi and antifungal drug discovery.

Biochemical, Transcriptional, and Bioinformatic Analysis of Lipid Droplets from Seeds of Date Palm (Phoenix dactylifera L.) and Their Use as Potent Sequestration Agents against the Toxic Pollutant, 2,3,7,8-Tetrachlorinated Dibenzo-p-Dioxin

“…This study reports the isolation, characterization, and deployment of date palm LDs as part of a possible broader biomimetic approach for removal of highly toxic organic hydrophobic pollutants, such as dioxins, from the environment. We use the term ‘biomimetic’ in view of a recently published study that described for the first time the presence of naturally occurring mechanism in fungi whereby LDs were shown to serve as sites for the sequestering of various types of lipophilic toxin ( Chang et al, 2015 ). As discussed below, this appears to be part of a wider detoxification role for LDs that may be present in a wide range of other species, including bacteria, algae, and maybe animals ( Gwak et al, 2014 ).…”

“…The overall concept of deploying LDs as agents to sequester lipophilic toxins has recently received validation from the natural world with reports that several fungal species employ cytosolic LDs for both defensive and aggressive purposes ( Chang et al, 2015 ). In one case, the endolichenic fungus, Phaeosphaeria sp.…”

“…In other cases, cells of the yeast species, Candida albicans and Saccharomyces cerevisiae , which contained elevated levels of LDs, manifested greatly enhanced resistance to phototoxicity by the plastoquinone derivative, hypocrellin A. These LDs acted as sites for the safe sequestration of hypocrellin A, in a location where it was no longer capable of generating harmful reactive oxidative species (ROS; Chang et al, 2015 ). These LD-rich fungi were also able to sequester externally applied toxic lipophilic agents, such as farnesol, amphotericin and micronazole, in a way that protected them from oxidative damage.…”

Lipid droplet functions beyond energy storage

“…A fungus residing asymptomatically inside lichens, Phaeosphaeria , can kill competing fungal species by producing toxic perylenequinones (PQs)[50]. PQs are toxic because light irradiation stimulates them to generate lethal levels of reactive oxygen species (ROS).…”

“…This and related detoxification functions for LDs may also have therapeutic implications. For example, some antifungal agents are more potent against yeast strains with defective LD biosynthesis [50]. Moreover, several drugs and prodrugs are known to accumulate in LDs [51, 52].…”