Ibuprofen antifungal activity on both planktonic and biofilm forms of fluconazole-resistant Candida spp. strains and its mechanism of action evaluated by flow cytometry

Abstract

Over the past few decades, researches have reported an increased incidence of invasive candidiasis and suggested that the majority of infections produced by this pathogen are associated with biofilm growth, which are more resistant to antimicrobial agents than planktonic cells. In addition to these problems, there are few antifungal agents available and it is necessary the development of novel therapeutic strategies. In that context, this study aimed to assess the antifungal potential of ibuprofen against fluconazole-resistant Candida spp. planktonic and biofilm forms proposing a new view to the drug that are used with other therapeutic indications. After 24 h, the fluconazole-resistant Candida spp. strains showed minimum inhibitory concentration (MIC) in the ranges of 1.5–3 mg/mL for ibuprofen by the broth microdilution method (M27-A3). According to our data by flow cytometry, ibuprofen cause fungal death after damaging the plasma and mitochondrial membrane associated to an increase of phosphatidylserine externalization which activates apoptotic signaling pathways. Regarding biofilm-forming isolates, ibuprofen promotes a reduction of viability cell in mature biofilm of Candida spp. (p<0.05). Therefore, it was concluded that ibuprofen is capable of inhibit the growth in vitro of Candida spp. fluconazole-resistant, both in planktonic as biofilm form, inducing cell death by apoptosis.