title: Biofilms formed by Candida albicans bloodstream isolates display phenotypic and transcriptional heterogeneity that are associated with resistance and pathogenicity.
abstract: BACKGROUND
  Candida albicans infections have become increasingly recognised as being biofilm related. Recent studies have shown that there is a relationship between biofilm formation and poor clinical outcomes in patients infected with biofilm proficient strains. Here we have investigated a panel of clinical isolates in an attempt to evaluate their phenotypic and transcriptional properties in an attempt to differentiate and define levels of biofilm formation.
  
  
  RESULTS
  Biofilm formation was shown to be heterogeneous; with isolates being defined as either high or low biofilm formers (LBF and HBF) based on different biomass quantification. These categories could also be differentiated using a cell surface hydrophobicity assay with 24 h biofilms. HBF isolates were more resistance to amphotericin B (AMB) treatment than LBF, but not voriconazole (VRZ). In a Galleria mellonella model of infection HBF mortality was significantly increased in comparison to LBF. Histological analysis of the HBF showed hyphal elements intertwined indicative of the biofilm phenotype. Transcriptional analysis of 23 genes implicated in biofilm formation showed no significant differential expression profiles between LBF and HBF, except for Cdr1 at 4 and 24 h. Cluster analysis showed similar patterns of expression for different functional classes of genes, though correlation analysis of the 4 h biofilms with overall biomass at 24 h showed that 7 genes were correlated with high levels of biofilm, including Als3, Eap1, Cph1, Sap5, Plb1, Cdr1 and Zap1.
  
  
  CONCLUSIONS
  Our findings show that biofilm formation is variable amongst C. albicans isolates, and categorising isolates depending on this can be used to predict how pathogenic the isolate will behave clinically. We have shown that looking at individual genes in less informative than looking at multiple genes when trying to categorise isolates at LBF or HBF. These findings are important when developing biofilm-specific diagnostics as these could be used to predict how best to treat patients infected with C. albicans. Further studies are required to evaluate this clinically.
authors.forename: Leighann
authors.initials: L
authors.lastname: Sherry
authors.forename: Ranjith
authors.initials: R
authors.lastname: Rajendran
authors.forename: David F
authors.initials: DF
authors.lastname: Lappin
authors.forename: Elisa
authors.initials: E
authors.lastname: Borghi
authors.forename: Federica
authors.initials: F
authors.lastname: Perdoni
authors.forename: Monica
authors.initials: M
authors.lastname: Falleni
authors.forename: Delfina
authors.initials: D
authors.lastname: Tosi
authors.forename: Karen
authors.initials: K
authors.lastname: Smith
authors.forename: Craig
authors.initials: C
authors.lastname: Williams
authors.forename: Brian
authors.initials: B
authors.lastname: Jones
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Nile
authors.affiliation: Infection and Immunity Research Group, Glasgow Dental School, School of Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, 378 Sauchiehall Street, Glasgow G2 3JZ, UK. gordon.ramage@glasgow.ac.uk.
authors.forename: Gordon
authors.initials: G
authors.lastname: Ramage
mesh_terms: D000666:Amphotericin B / Q000494:pharmacology; D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology; D018441:Biofilms / Q000254:growth & development*; D001681:Biological Assay; D002176:Candida albicans / Q000235:genetics* / Q000302:isolation & purification / Q000472:pathogenicity / Q000502:physiology*; D058387:Candidemia / Q000382:microbiology; D025141:Drug Resistance, Fungal; D020869:Gene Expression Profiling; D014644:Genetic Variation; D006801:Humans; D007915:Lepidoptera / Q000382:microbiology; D011743:Pyrimidines / Q000494:pharmacology; D016019:Survival Analysis; D014230:Triazoles / Q000494:pharmacology; D014774:Virulence; D065819:Voriconazole
chemical_list: D000935:Antifungal Agents; D011743:Pyrimidines; D014230:Triazoles; D000666:Amphotericin B; D065819:Voriconazole