Abstract
The glucocorticoid betamethasone (BM) has potent anti-inflammatory and immunosuppressive effects; however, it increases the susceptibility of patients to superficial Candida infections. Previously we found that this disadvantageous side effect can be counteracted by menadione sodium bisulfite (MSB) induced oxidative stress treatment. The fungus specific protein phosphatase Z1 (CaPpz1) has a pivotal role in oxidative stress response of Candida albicans and was proposed as a potential antifungal drug target. The aim of this study was to investigate the combined effects of CaPPZ1 gene deletion and MSB treatment in BM pre-treated C. albicans cultures. We found that the combined treatment increased redox imbalance, enhanced the specific activities of antioxidant enzymes, and reduced the growth in cappz1 mutant (KO) strain. RNASeq data demonstrated that the presence of BM markedly elevated the number of differentially expressed genes in the MSB treated KO cultures. Accumulation of reactive oxygen species, increased iron content and fatty acid oxidation, as well as the inhibiting ergosterol biosynthesis and RNA metabolic processes explain, at least in part, the fungistatic effect caused by the combined stress exposure. We suggest that the synergism between MSB treatment and CaPpz1 inhibition could be considered in developing of a novel combinatorial antifungal strategy accompanying steroid therapy.
Highlights
Betamethasone (BM) is an effective anti-inflammatory, immunosuppressive, vasoconstriction and antiproliferative agent widely used in various medical treatments [1,2].increased susceptibility to superficial and invasive Candida infections has been reported in these BM-based therapies [1,3]
The interaction between BM and menadione sodium bisulfite (MSB) was studied on C. albicans biofilms by a two-dimensional broth microdilution chequerboard assay on one-day-old biofilms after
According to our results the steroid has no detectable effects on the pathogen, but makes it more sensitive to oxidative stress generated by MSB [8,9]
Summary
Betamethasone (BM) is an effective anti-inflammatory, immunosuppressive, vasoconstriction and antiproliferative agent widely used in various medical treatments [1,2].increased susceptibility to superficial and invasive Candida infections has been reported in these BM-based therapies [1,3]. Betamethasone (BM) is an effective anti-inflammatory, immunosuppressive, vasoconstriction and antiproliferative agent widely used in various medical treatments [1,2]. Long-lasting treatment of asthma bronchiale and chronic pulmonary disease with inhaled glucocorticoids is a potential risk for the development of oral candidiasis [4]. Glucocorticoid therapies promote candidiasis in patients who suffer from acute renal failure, cancerous disease, systemic lupus erythematosus or who have undergone bone-marrow or solid-organ transplantation [1,3,5,6]. New alternative therapeutic approaches are urgently needed to improve the efficiency of anti-Candida medication and hereby maintain the quality of life of glucocorticoid-treated patients
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