title: The Role of Isocitrate Lyase (ICL1) in the Metabolic Adaptation ofCandida albicansBiofilms.
abstract: BACKGROUND
  A major characteristic ofCandidabiofilm cells that differentiates them from free-floating cells is their high tolerance to antifungal drugs. This high resistance is attributed to particular biofilm properties, including the accumulation of extrapolymeric substances, morphogenetic switching, and metabolic flexibility.
  
  
  OBJECTIVE
  This study evaluated the roles of metabolic processes (in particular the glyoxylate cycle) on biofilm formation, antifungal drug resistance, morphology, and cell wall components.
  
  
  METHODS
  Growth, adhesion, biofilm formation, and cell wall carbohydrate composition were quantified for isogenicCandida albicansICL1/ICL1, ICL1/icl1, andicl1/icl1strains. The morphology and topography of these strains were compared by light microscopy and scanning electron microscopy.FKS1(glucan synthase),ERG11(14-α-demethylase), andCDR2(efflux pump) mRNA levels were quantified using qRT-PCR.
  
  
  RESULTS
  The ICL1/icl1 andicl1/icl1strains formed similar biofilms and exhibited analogous drug-tolerance levels to the control ICL1/ICL1 strains. Furthermore, the drug sequestration ability of β-1, 3-glucan, a major carbohydrate component of the extracellular matrix, was not impaired. However, the inactivation of ICL1 did impair morphogenesis. ICL1 deletion also had a considerable effect on the expression of theFKS1,ERG11, andCDR2genes.FKS1andERG11were upregulated in ICL1/icl1andicl1/icl1cells throughout the biofilm developmental stages, andCDR2was upregulated at the early phase. However, their expression was downregulated compared to the control ICL1/ICL1 strain.
  
  
  CONCLUSIONS
  We conclude that the glyoxylate cycle is not a specific determinant of biofilm drug resistance.
authors: Infectomics Cluster, Advanced Medical and Dental Institute, Universiti Sains Malaysia, Malaysia.
authors: Oluwaseun Ayodeji
authors: OA
authors: Ishola
authors: Infectomics Cluster, Advanced Medical and Dental Institute, Universiti Sains Malaysia, Malaysia.
authors: Seng Yeat
authors: SY
authors: Ting
authors: Infectomics Cluster, Advanced Medical and Dental Institute, Universiti Sains Malaysia, Malaysia.
authors: Yasser M
authors: YM
authors: Tabana
authors: Infectomics Cluster, Advanced Medical and Dental Institute, Universiti Sains Malaysia, Malaysia.
authors: Mowaffaq Adam
authors: MA
authors: Ahmed
authors: Infectomics Cluster, Advanced Medical and Dental Institute, Universiti Sains Malaysia, Malaysia.
authors: Muhammad Amir
authors: MA
authors: Yunus
authors: Regenerative Medicine Cluster, Advanced Medical and Dental Institute, Universiti Sains Malaysia, Malaysia.
authors: Rafeezul
authors: R
authors: Mohamed
authors: Department of Medical Microbiology and Parasitology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Selangor, Malaysia.
authors: Leslie Thian
authors: LT
authors: Lung Than
authors: Infectomics Cluster, Advanced Medical and Dental Institute, Universiti Sains Malaysia, Malaysia.
authors: Doblin
authors: D
authors: Sandai
keywords: Biofilms; Candida albicans; Isocitrate Lyase (ICL1); Resistance