Could Malassezia yeasts be implicated in skin carcinogenesis through the production of aryl-hydrocarbon receptor ligands?

UNLABELLED Malassezia yeasts are found on the skin of all humans and many warm-blooded animals. In vitro they have the ability to synthesize potent ligands (indolo[3,2-b]carbazole, malassezin and indirubin) of the aryl-hydrocarbon receptor (AhR; synonym: dioxin receptor) when the sweat contained L-tryptophan is used as the single nitrogen source. The production of these AhR-ligands has been associated with pathogenic strains of a certain Malassezia species (Malassezia furfur) but recent evidence shows that this property is widely distributed in almost all currently known Malassezia species. AhR is associated with carcinogenesis and the potential connection of these ubiquitous skin symbionts, and putative pathogens, with skin neoplasia should be evaluated mainly focusing on mechanisms related to the distinctive ability of the yeast to produce potent AhR ligands. HYPOTHESIS Synthesis of available pertinent data show a possible link between Malassezia produced AhR ligands and skin carcinogenesis, particularly of basal cell carcinoma (BCC). BCCs are almost exclusively observed in animal species colonized by Malassezia. In humans and animals there is overlapping in the skin regions colonized by this yeast and affected by BCC. The potent AhR ligands synthesized by pathogenic Malassezia strains could contribute to tumor promotion by: modification of the UV radiation carcinogenesis, alterations in the salvage/survival of initiated tumor cells, inhibition of cell senescence, interaction with vitamin D metabolism, promotion of immune tolerance and finally pro-carcinogenic modulation of cell cycle progression and apoptosis.