Selektif Serotonin Geri Alım İnhibitörlerinin Tek Başına ve Flukonazol ile Kombinasyonlarının Antifungal ve Antibiyofilm Aktiviteleri

Antifungal and Antibiofilm Activities of Selective Serotonin Reuptake Inhibitors Alone and in Combination with Fluconazole

YAMAÇ TEKİNTAŞ,AYBALA TEMEL,Ayşegül ATEŞ,Bayrı ERAÇ,Dilek Yeşim METİN,Süleyha Hilmioğlu POLAT,Mine HOŞGÖR LİMONCU

Abstract

Amaç: Klinik açıdan önemli fungal patojenlerden olan Candida türleri, biyofilm üretme kapasiteleriyle tedavide zorluklara yol açmaktadır. Antifungal direnç oranları ve yeni antifungallerin keşfinin sınırlılığı göz önüne alındığında, farklı terapötik amaç için kullanılan çeşitli ilaç moleküllerinin antifungal ve antibiyofilm etkileri daha fazla önem kazanmaktadır. Çalışmamızın amacı, selektif serotonin geri alım inhibitörleri (SSRI) olan sertralin (SRT), paroksetin (PRX), fluoksetinin (FLX), tek başına ve flukonazol (FLC) ile kombine halde Candida türlerine karşı antifungal ve antibiyofilm etkilerinin belirlenmesidir

Özet

Objectives: Candida spp. are clinically important pathogens that cause difficulties for treatment by biofilm formation. Considering antifungalresistance rates and the limitations in the discovery of new antifungals, the antifungal and antibiofilm effects of various drugs used for differenttherapeutic purposes are becoming more important. The goal of our study was to determine the antifungal and antibiofilm effects of the selectiveserotonin reuptake inhibitors (SSRIs), namely sertraline (SRT), paroxetine (PRX), and fluoxetine (FLX) alone and in combination with fluconazole(FLC) against Candida spp.Materials and Methods: Twenty Candida spp. strains isolated from clinical samples from Ege University Hospital were identified by the Dalmaumethod and matrix-assisted laser desorption ionization time of flight mass spectrometry. The minimum inhibitory concentrations (MICs) of the SSRIsand FLC were detected by broth microdilution method. Synergistic interactions between the SSRIs and FLC were investigated by checkerboardassay. The antibiofilm effects of the SSRIs were determined by spectrophotometric microplate method.Results: Among the isolates, five different Candida spp. (C. albicans, C. glabrata, C. krusei, C. tropicalis, and C.parapsilosis) were identified. The MICsof the SSRIs ranged between 16-512 µg/mL. While SRT showed the highest antifungal effect, the antibiofilm efficacy of FLX was higher than that ofthe other agents. Moreover, FLX and PRX showed a synergistic effect with FLC in 13 and 19 isolates, respectively. Four isolates were strong biofilmproducers while nine isolates were moderate biofilm producers. C. parapsilosis strains showed higher biofilm production than the other species.At MIC/2 concentration, FLX and SRT alone inhibited mature biofilms in six and five isolates, respectively, while PRX caused increases biofilmformation in seven isolates.Conclusion: This study revealed that MIC/2 concentrations of SSRIs could have antifungal and antibiofilm effects. SRT and FLX alone or incombination with antifungals may possibly have therapeutic potential for combating fungal infections.