Is fungal A-PCD the Achilles heel of plant and human killer pathogens?

Apoptotic-like programmed cell death (A-PCD) has emerged as an important mechanism, involved in and affecting fungal development, survival, and pathogenicity. This talk will examine fungal A-PCD in a retrospective to prospective point of view, with emphasis on the role of A-PCD in pathogenicity.

Studies in the late 90s first revealed that yeasts undergo cell death with similar phenotypes to mammalian apoptosis. While the necessity of a suicidal machinery in a single-cell organism remained controversial, studies in filamentous species supported the existence of an operative A-PCD machinery, which has been associated with stress adaptation, development, and pathogenicity. In the necrotrophic plant pathogen Botrytis cinerea, A-PCD was observed during the establishment phase, and the protective role of the anti-A-PCD protein BcBir1 was found be necessary for virulence of this fungus. Similar findings were recently found in the human pathogen Aspergillus fumigatus. In both cases, the host immune response, while very different, initiated A-PCD in the pathogen as a defense strategy. The components of the A-PCD machinery are therefore potential targets for antifungal drugs that will trigger A-PCD. Indeed, genome search for potential candidates reveals a repertoire of putative fungal homologues of known apoptosis-related proteins; however, analyses of these homologues showed a surprisingly low level of functional conservation. Furthermore, domain search and in-depth genome analyses showed that fungi lack the entire upstream parts of animal apoptotic machinery, and miss most of the important apoptotic domains. Hence, while similar in phenotype, fungal A-PCD seems substantially different in regulation and mechanism from animal apoptosis. Recent studies support the involvement of mitochondria homeostasis and metabolism in regulation of fungal A-PCD, but further investigation is necessary in order to gain better insight of the process and identify key A-PCD regulators that might be used as targets for A-PCD-inducing antifungal drugs