Biofilms formed by Candida albicans bloodstream isolates display phenotypic and transcriptional heterogeneity that are associated with resistance and pathogenicity

Leighann Sherry, Ranjith Rajendran, David F Lappin, Elisa Borghi, Federica Perdoni, Monica Falleni, Delfina Tosi, Karen Smith, Craig Williams, Brian Jones, Chris J Nile, Gordon Ramage

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)182
JournalBMC Microbiology
Volume14
DOIs
Publication statusPublished - 5 Jul 2014

Fingerprint

Biofilms
Candida albicans
Virulence
Genes
Biomass
Amphotericin B
Infection
Hydrophobic and Hydrophilic Interactions
Cluster Analysis

Keywords

  • Amphotericin B
  • Animals
  • Antifungal Agents
  • Biofilms
  • Biological Assay
  • Candida albicans
  • Candidemia
  • Drug Resistance, Fungal
  • Gene Expression Profiling
  • Genetic Variation
  • Humans
  • Lepidoptera
  • Pyrimidines
  • Survival Analysis
  • Triazoles
  • Virulence
  • Voriconazole

Cite this

Sherry, Leighann ; Rajendran, Ranjith ; Lappin, David F ; Borghi, Elisa ; Perdoni, Federica ; Falleni, Monica ; Tosi, Delfina ; Smith, Karen ; Williams, Craig ; Jones, Brian ; Nile, Chris J ; Ramage, Gordon. / Biofilms formed by Candida albicans bloodstream isolates display phenotypic and transcriptional heterogeneity that are associated with resistance and pathogenicity. In: BMC Microbiology. 2014 ; Vol. 14. pp. 182.
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Biofilms formed by Candida albicans bloodstream isolates display phenotypic and transcriptional heterogeneity that are associated with resistance and pathogenicity. / Sherry, Leighann; Rajendran, Ranjith; Lappin, David F; Borghi, Elisa; Perdoni, Federica; Falleni, Monica; Tosi, Delfina; Smith, Karen; Williams, Craig; Jones, Brian; Nile, Chris J; Ramage, Gordon.

In: BMC Microbiology, Vol. 14, 05.07.2014, p. 182.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Biofilms formed by Candida albicans bloodstream isolates display phenotypic and transcriptional heterogeneity that are associated with resistance and pathogenicity

AU - Sherry, Leighann

AU - Rajendran, Ranjith

AU - Lappin, David F

AU - Borghi, Elisa

AU - Perdoni, Federica

AU - Falleni, Monica

AU - Tosi, Delfina

AU - Smith, Karen

AU - Williams, Craig

AU - Jones, Brian

AU - Nile, Chris J

AU - Ramage, Gordon

PY - 2014/7/5

Y1 - 2014/7/5

N2 - 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.

AB - 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.

KW - Amphotericin B

KW - Animals

KW - Antifungal Agents

KW - Biofilms

KW - Biological Assay

KW - Candida albicans

KW - Candidemia

KW - Drug Resistance, Fungal

KW - Gene Expression Profiling

KW - Genetic Variation

KW - Humans

KW - Lepidoptera

KW - Pyrimidines

KW - Survival Analysis

KW - Triazoles

KW - Virulence

KW - Voriconazole

U2 - 10.1186/1471-2180-14-182

DO - 10.1186/1471-2180-14-182

M3 - Article

VL - 14

SP - 182

JO - BMC Microbiology

JF - BMC Microbiology

SN - 1471-2180

ER -