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Cellular conditions that modulate the fungicidal activity of occidiofungin
Author(s) -
Robinson C.A.,
Denison C.,
Burkenstock A.,
Nutter C.,
Gordon D.M.
Publication year - 2017
Publication title -
journal of applied microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.889
H-Index - 156
eISSN - 1365-2672
pISSN - 1364-5072
DOI - 10.1111/jam.13496
Subject(s) - candida albicans , saccharomyces cerevisiae , calcineurin , biology , extracellular , candida glabrata , calcium , microbiology and biotechnology , corpus albicans , yeast , cycloheximide , calmodulin , biochemistry , enzyme , chemistry , protein biosynthesis , medicine , surgery , organic chemistry , transplantation
Aims To identify cellular conditions that significantly alter susceptibility of Saccharomyces cerevisiae , Candida albicans and Candida glabrata to the antimicrobial peptide, occidiofungin. Methods and Results Genetic and pharmacological approaches were used to determine a role for calcium signalling in occidiofungin sensitivity profiles for S. cerevisiae , C. albicans and C. glabrata strains of yeast. Minimum inhibitory concentration (MIC) and drop assays found that extracellular calcium resulted in a fourfold resistance, and this was independent of an intact calmodulin–calcineurin signalling pathway. A similar resistance was found in the presence of magnesium but not other cations. Occidiofungin was found to be ineffective against cells in a quiescent state when measured by MIC, drop assay and short‐term time‐kill assays. A similar resistance pattern was detected for S. cerevisiae cultures pre‐exposed to cycloheximide or placed in depleted media conditions. Conclusions Extracellular calcium results in fungal tolerance to occidiofungin bioactivity outside of the calmodulin–calcineurin pathway. In addition, the resistance of quiescent cells suggests that active cellular growth is a requirement for occidiofungin's mechanism of action. Significance and Impact of the Study The identification of cellular conditions that have a role in the activity of occidiofungin provided insight into potential cellular targets of this novel antifungal.