title: Acetylsalicylic acid (aspirin) reduces damage to reconstituted human tissues infected with Candida species by inhibiting extracellular fungal lipases.
abstract: A reconstituted human tissue model was used to mimic Candida albicans and Candida parapsilosis infection in order to investigate the protective effects of acetylsalicylic acid (aspirin, ASA). We found that therapeutic concentrations of ASA reduced tissue damage in the in vitro infection model. We further evaluated the lipase inhibitory effects of ASA by investigating the growth of C. albicans, C. parapsilosis and C. parapsilosis lipase negative (Deltacplip1-2/Deltacplip1-2) mutants in a lipid rich minimal medium supplemented with olive oil and found that a therapeutic concentration of ASA inhibited the growth of wild type fungi. The lipase inhibitors quinine and ebelactone B were also shown to reduce growth and protect against tissue damage from Candida species, respectively. A lipolytic activity assay also showed that therapeutic concentrations of ASA inhibited C. antarctica and C. cylindracea purified lipases obtained through a commercial kit. The relationship between ASA and lipase was characterized through a computed structural model of the Lipase-2 protein from C. parapsilosis in complex with ASA. The results suggest that development of inhibitors of fungal lipases could result in broad-spectrum therapeutics, especially since fungal lipases are not homologous to their human analogues.
authors.affiliation: Department of Medicine, Division of Infectious Diseases, Albert Einstein College of Medicine, 1300 Morris Park Avenue, NY 10461, USA.
authors.forename: David
authors.initials: D
authors.lastname: Trofa
authors.forename: Mariangela
authors.initials: M
authors.lastname: Agovino
authors.forename: Frank
authors.initials: F
authors.lastname: Stehr
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Schäfer
authors.forename: Dmitry
authors.initials: D
authors.lastname: Rykunov
authors.forename: András
authors.initials: A
authors.lastname: Fiser
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Hamari
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Nosanchuk
authors.forename: Attila
authors.initials: A
authors.lastname: Gácser
mesh_terms: D001241:Aspirin / Q000494:pharmacology*; D002175:Candida / Q000145:classification / Q000187:drug effects* / Q000201:enzymology / Q000472:pathogenicity*; D002176:Candida albicans / Q000187:drug effects / Q000201:enzymology; D002177:Candidiasis / Q000382:microbiology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D004848:Epithelium / Q000254:growth & development / Q000382:microbiology*; D005656:Fungal Proteins / Q000037:antagonists & inhibitors*; D006801:Humans; D008049:Lipase / Q000037:antagonists & inhibitors*; D009055:Mouth / Q000166:cytology*
chemical_list: D005656:Fungal Proteins; D008049:Lipase; D001241:Aspirin
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