Metabolic Adaptation Of Candida Albicans Biofilms

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Date
2015-02
Authors
Ayodeji, Ishola Oluwaseun
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Publisher
Universiti Sains Malaysia
Abstract
Fungal biofilms have high clinical importance. A notable one is Candida albicans biofilm, whose importance is attributed to its ability to institute new and reoccurring infections, accounting for about 40% of disseminated candidiasis. The major characteristic of biofilms which differentiates it from planktonic cells is its high tolerance to treatments and the immune system. Sessile growths have been reported to be several folds resistant to the minimum inhibitory concentration (MIC) of free floating cells drug treatment, and consequently frustrating the efficacy of drugs. The high resistivity is attributed to distinctive properties including accumulation of extrapolymeric substance (EPS), phenotypic adaptation switch and metabolic flexibility among others. In this study, the influential roles of metabolism physiology, particularly glyoxylate pathway Isocitrate lyase (ICL) enzyme on biofilm formation, resistivity, morphology, and cell wall components were evaluated. It was interesting to find that, heterozygous and homozygous ICL1 mutant strains formed biofilm and exhibited a high tolerance level similar to the reference strain. The enzyme ICL impaired dimorphism trait as observed in mutant strains. Furthermore, sequestrating ability of beta-1, 3-glucan, a major carbohydrate component of the extracellular matrix (ECM) was not impaired. Deletion of ICL conferred a considerable effect on glucan synthase pathway FKS1, gene encoding 14-α-demethylase enzyme necessary for lanosterol conversion to ergosterol ERG11 and efflux pump gene CDR2 transcription. FKS1 and ERG11 were up regulated throughout the developmental stages; CDR2 was up regulated at the early phase. However, expression was down regulated compared to the reference strain. Therefore, Glyoxylate pathway is not a specific determinant of biofilm resistivity, but essential for its survival. This study serves as a foundation for future experimental investigation of sole and synergistic alternative pathways interactions for potential drug targets.
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Biofilm
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