title: Non-steroidal anti-inflammatory drugs may modulate the protease activity of Candida albicans.
abstract: The phenotypic pressure exerted by non-steroidal anti-inflammatory drugs (NSAIDs) on autochthonous and pathogenic microbiota remains sparsely known. In this study, we investigated if some NSAIDs increment or diminish the secretion of aspartyl-proteases (Sap) by Candida albicans grown under different phenotypes and oxygen availability using a set of SAP knock-out mutants and other set for genes (EFG1 and CPH1) that codify transcription factors involved in filamentation and protease secretion. Pre-conditioned cells were grown under planktonic and biofilm phenotypes, in normoxia and anoxia, in the presence of plasma concentrations of acetylsalicylic acid, diclofenac, indomethacin, nimesulide, piroxicam, ibuprofen, and acetaminophen. For diclofenac, indomethacin, nimesulide, and piroxicam the secretion rates of Sap by SAP1-6, EFG1, and CPH1 mutants were similar or, even, inferior to parental wild-type strain. This suggests that neither Sap 1-6 isoenzymes nor Efg1/Cph1 pathways may be entirely responsible for protease release when exposed to these NSAIDs. Ibuprofen and acetaminophen enhanced Sap secretion rates in three environmental conditions (normoxic biofilm, normoxic planktonic and anoxic planktonic). In other hand, aspirin seems to reduce the Sap-related pathogenic behavior of candidal biofilms. Modulation of Sap activity may occur according to candidal phenotypic state, oxygen availability, and type of NSAID to which the cells are exposed.
authors: Xenobiotics Research Unity, Biological and Health Sciences Centre, The Pontifical Catholic University of Paraná, Rua Imaculada Conceição 1155, Curitiba, Brazil.
authors: Alessandra P
authors: AP
authors: Carvalho
authors: Lauren C
authors: LC
authors: Gursky
authors: Rosimeire T
authors: RT
authors: Rosa
authors: Alinne U M
authors: AU
authors: Rymovicz
authors: Patrícia M S
authors: PM
authors: Campelo
authors: Ana Maria T
authors: AM
authors: Grégio
authors: Cristiane Y
authors: CY
authors: Koga-Ito
authors: Lakshman P
authors: LP
authors: Samaranayake
authors: Edvaldo A R
authors: EA
authors: Rosa
mesh_terms: D000332:Aerobiosis; D000693:Anaerobiosis; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D057055:Aspartic Acid Proteases / Q000378:metabolism*; D018441:Biofilms / Q000187:drug effects* / Q000254:growth & development; D002176:Candida albicans / Q000187:drug effects* / Q000201:enzymology* / Q000254:growth & development; D005656:Fungal Proteins / Q000378:metabolism*; D006801:Humans; D021381:Protein Transport / Q000187:drug effects; D014774:Virulence
chemical_list: D000893:Anti-Inflammatory Agents; D005656:Fungal Proteins; D057055:Aspartic Acid Proteases