title: Mitochondria and fungal pathogenesis: drug tolerance, virulence, and potential for antifungal therapy.
abstract: Recently, mitochondria have been identified as important contributors to the virulence and drug tolerance of human fungal pathogens. In different scenarios, either hypo- or hypervirulence can result from changes in mitochondrial function. Similarly, specific mitochondrial mutations lead to either sensitivity or resistance to antifungal drugs. Here, we provide a synthesis of this emerging field, proposing that mitochondrial function in membrane lipid homeostasis is the common denominator underlying the observed effects of mitochondria in drug tolerance (both sensitivity and resistance). We discuss how the contrasting effects of mitochondrial dysfunction on fungal drug tolerance and virulence could be explained and the potential for targeting mitochondrial factors for future antifungal drug development.
authors.affiliation: Department of Biochemistry and Molecular Biology, Monash University, Clayton 3800, Victoria, Australia.
authors.forename: Miguel
authors.initials: M
authors.lastname: Shingu-Vazquez
authors.forename: Ana
authors.initials: A
authors.lastname: Traven
mesh_terms: D000935:Antifungal Agents / Q000378:metabolism / Q000494:pharmacology*; D001393:Azoles / Q000494:pharmacology; D002176:Candida albicans / Q000187:drug effects / Q000378:metabolism / Q000472:pathogenicity; D041221:Candida glabrata / Q000187:drug effects / Q000378:metabolism / Q000472:pathogenicity; D003455:Cryptococcus neoformans / Q000187:drug effects / Q000378:metabolism / Q000472:pathogenicity; D055808:Drug Discovery; D025141:Drug Resistance, Fungal / Q000235:genetics; D005658:Fungi / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D006801:Humans; D008563:Membrane Lipids / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D008928:Mitochondria / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D051336:Mitochondrial Membranes / Q000378:metabolism*; D009181:Mycoses / Q000188:drug therapy* / Q000382:microbiology; D011090:Polyenes / Q000494:pharmacology; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000378:metabolism / Q000472:pathogenicity
chemical_list: D000935:Antifungal Agents; D001393:Azoles; D008563:Membrane Lipids; D011090:Polyenes