Metabolic Adaptation Of Candida Albicans Biofilms
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Date
2015-02
Authors
Ayodeji, Ishola Oluwaseun
Journal Title
Journal ISSN
Volume Title
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.
Description
Keywords
Biofilm