Acetylsalicylic acid (aspirin) reduces damage to reconstituted human tissues infected with Candida species by inhibiting extracellular fungal lipases

David Trofa, Mariangela Agovino, Frank Stehr, Wilhelm Schäfer, Dmitry Rykunov, András Fiser, Zsuzsanna Hamari, Joshua D. Nosanchuk, Attila Gácser

Research output: Contribution to journalArticle

16 Citations (Scopus)

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 (Δcplip1-2/Δcplip1-2) 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.

Original languageEnglish
Pages (from-to)1131-1139
Number of pages9
JournalMicrobes and Infection
Volume11
Issue number14-15
DOIs
Publication statusPublished - Dec 1 2009

Keywords

  • Acetylsalicylic acid
  • Candida
  • Human fungal pathogen
  • Inhibition
  • Lipases
  • Pathogenesis
  • Yeast

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Infectious Diseases

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