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Tétel Korlátozottan hozzáférhető Genetic and phenotypic investigation of antimycotic resistance in probiotic yeastsAtalah, Hadeer; Valter, Péter Pfliegler; DE--Természettudományi és Technológiai Kar--Biológiai és Ökológiai IntézetSuccessively, S. cerevisiae has been extensively studied for food microbiological and biotechnological purposes. Moreover, during the last decade, commercialized S. cerevisiae has brought an increasing interest for involving in the probiotic industry as a lyophilized form of S. boulardii, a subtype of S. cerevisiae. Due to the possession of many properties, S. boulardii has been used as a preventive and therapeutic agent for human GI disorders and bacterial diarrhea. It also was advised during antibiotic therapies to inhibit first episodes of Clostridium difficile-associated diarrhea. Although S. boulardii probiotic regarded as a safe product, severe systemic infections have been announced because of opportunistic strains. Complications of colonization of pathogenic S. boulardii in the bloodstream and some organs have risen the risk of prescribing S. boulardii probiotic, especially for immunocompetent patients. Due to the increasing spread of severe infections from S. boulardii virulence strains, they have now been considered as a main emergent pathogen (De Llanos et al., 2006). The issue of fungemia and invasive infections induced by S. cerevisiae (boulardii) has headed the health concerns with an elevating number of related publications since 1990s (Sulik-Tyszka et al., 2018); particularly after publishing some hospitalization studies of fungal outbreaks (Cassone et al., 2003). S. boulardii causing infections has been reported among intensive care unit (ICU) patients and in otherwise healthy individuals. For years, azoles and polyenes derivatives are the drugs of choice to control the burden of serious fungal diseases associated with S. boulardii. However, nowadays, unusual fungal responses to antimycotic drugs were observed. Recently, a growing number of publications indicated that S. boulardii strains have obtained tolerance to the MIC of antifungal agents while resistance traits are coded by many colonies. For the sake of increasing reports of infections caused by S. boulardii and its tolerance to antifungals, it is important to elevate the awareness of prescribing yeast probiotic, especially to immunocompromised patients and it should not be considered risk-free (Thygesen et al., 2012). In the present study, three S. boulardii blood isolates obtained from the university clinic and four commercial S. boulardii strains have been examined under the influence of FLC and AmB with various concentration series to observe their growth in challenging environments. It was demonstrated that yeasts from the same specie exhibit various responses to the antifungals, and 32 most importantly that some highly resistant colonies were grown at high stock concentrations. Isolates that response differently to the same toxicity status should undergo further studies to promote suitable drug doses for infected patients. Phenotypic features of the yeast samples used here were different in the toxic environment indicating various gene expression. Thus, CNVs of the genes responsible for resistance have been compared in the seven samples. Among them, there was no considerable difference in the resistance genes copy number. To explain the heterogeneity response of the samples, gene expression and mutations should be listed for further examinations. The observed highly resistant cells in stressful petri dishes could be a result of the emergence of unresponsive subpopulations in the samples; so-called heteroresistance phenomena. A visualization for the strain/isolate genetic sequencing in YMAP tool was helpful in detecting regions with heterozygosity, homozygosity, and CNVs of resistance genes. Most of the strains and isolates displayed heterozygosity regions across chromosomes, which meant that those samples have undergone genetic variations driven by many factors. It can be concluded that evolutionary dynamics of S. boulardii have now overcome the challenged limits of surviving. Accordingly, current medical recommendations suggest S. boulardii infections as an issue that should not be ignored.