Exposure of Candida albicans to antifungal agents affects expression of SAP2 and SAP9 secreted proteinase genes

Vanessa M S Copping; Caroline Barelle; Bernhard Hube; Neil A R Gow; Alistair J P Brown; Frank C Odds

doi:10.1093/jac/dki088

Exposure of Candida albicans to antifungal agents affects expression of SAP2 and SAP9 secreted proteinase genes

Vanessa M S Copping, Caroline Barelle, Bernhard Hube, Neil A R Gow, Alistair J P Brown, Frank C Odds

Medical Sciences

Research output: Contribution to journal › Article › peer-review

86 Citations (Scopus)

Abstract

Objectives: To ascertain the effects of subinhibitory concentrations of several antifungal agents on a virulence factor: secreted proteinase (Sap) activity and expression of SAP genes in Candida albicans.

Methods: Enzyme assays and growth measurements, GFP-SAP2 promoter constructs and fluorescence measurement, transcript profiling and RT-PCR.

Results: For seven of eight C. albicans isolates tested, exposure to fluconazole gave an increase in Sap specific activity; for one isolate, resistant to azoles and flucytosine, fluconazole exposure led to a fall in Sap activity. A similar relationship between growth reduction and increased Sap activity was seen with C. albicans cells treated with subinhibitory concentrations of itraconazole, miconazole, flucytosine and caspofungin. Transcript profiling indicated antifungal exposure was associated with increased expression of mRNA from SAP2 and SAP9 genes; this was confirmed for fluconazole and caspofungin exposure by RT-PCR.

Conclusions: Antifungal agents with three different mechanisms of action similarly generate a rise in expression of SAP2 and activity of the secreted Sap2 gene product, a known virulence factor, in most isolates of C. albicans. One isolate of the fungus showed an opposite response.

Original language	English
Pages (from-to)	645-654
Number of pages	10
Journal	Journal of Antimicrobial Chemotherapy
Volume	55
Issue number	5
Early online date	8 Apr 2005
DOIs	https://doi.org/10.1093/jac/dki088
Publication status	Published - May 2005

Keywords

Antifungal Agents
Aspartic Acid Endopeptidases
Azoles
Candida albicans
Echinocandins
Flucytosine
Fungal Proteins
Gene Expression Profiling
Gene Expression Regulation, Fungal
Green Fluorescent Proteins
Humans
Microbial Sensitivity Tests
Oligonucleotide Array Sequence Analysis
Peptides, Cyclic
Recombinant Fusion Proteins
Virulence Factors
Fluconazole
Caspofungin
Itraconazole
Amphotericin B
Virulence genes
Virulence
Aspartyl Proteinases
Subinhibitory concentrations
In-vitro
Adhesion
Phagocytosis
Macrophage

Access to Document

10.1093/jac/dki088

http://jac.oxfordjournals.org/content/55/5/645

Cite this

@article{3228e32a436f4afeb050fc8b5b1233a9,

title = "Exposure of Candida albicans to antifungal agents affects expression of SAP2 and SAP9 secreted proteinase genes",

abstract = "Objectives: To ascertain the effects of subinhibitory concentrations of several antifungal agents on a virulence factor: secreted proteinase (Sap) activity and expression of SAP genes in Candida albicans.Methods: Enzyme assays and growth measurements, GFP-SAP2 promoter constructs and fluorescence measurement, transcript profiling and RT-PCR.Results: For seven of eight C. albicans isolates tested, exposure to fluconazole gave an increase in Sap specific activity; for one isolate, resistant to azoles and flucytosine, fluconazole exposure led to a fall in Sap activity. A similar relationship between growth reduction and increased Sap activity was seen with C. albicans cells treated with subinhibitory concentrations of itraconazole, miconazole, flucytosine and caspofungin. Transcript profiling indicated antifungal exposure was associated with increased expression of mRNA from SAP2 and SAP9 genes; this was confirmed for fluconazole and caspofungin exposure by RT-PCR.Conclusions: Antifungal agents with three different mechanisms of action similarly generate a rise in expression of SAP2 and activity of the secreted Sap2 gene product, a known virulence factor, in most isolates of C. albicans. One isolate of the fungus showed an opposite response.",

keywords = "Antifungal Agents, Aspartic Acid Endopeptidases, Azoles, Candida albicans, Echinocandins, Flucytosine, Fungal Proteins, Gene Expression Profiling, Gene Expression Regulation, Fungal, Green Fluorescent Proteins, Humans, Microbial Sensitivity Tests, Oligonucleotide Array Sequence Analysis, Peptides, Cyclic, Recombinant Fusion Proteins, Virulence Factors, Fluconazole , Caspofungin, Itraconazole, Amphotericin B, Virulence genes, Virulence , Aspartyl Proteinases, Subinhibitory concentrations, In-vitro , Adhesion, Phagocytosis, Macrophage",

author = "Copping, {Vanessa M S} and Caroline Barelle and Bernhard Hube and Gow, {Neil A R} and Brown, {Alistair J P} and Odds, {Frank C}",

year = "2005",

month = may,

doi = "10.1093/jac/dki088",

language = "English",

volume = "55",

pages = "645--654",

journal = "Journal of Antimicrobial Chemotherapy",

issn = "0305-7453",

publisher = "Oxford University Press",

number = "5",

}

TY - JOUR

T1 - Exposure of Candida albicans to antifungal agents affects expression of SAP2 and SAP9 secreted proteinase genes

AU - Copping, Vanessa M S

AU - Barelle, Caroline

AU - Hube, Bernhard

AU - Gow, Neil A R

AU - Brown, Alistair J P

AU - Odds, Frank C

PY - 2005/5

Y1 - 2005/5

N2 - Objectives: To ascertain the effects of subinhibitory concentrations of several antifungal agents on a virulence factor: secreted proteinase (Sap) activity and expression of SAP genes in Candida albicans.Methods: Enzyme assays and growth measurements, GFP-SAP2 promoter constructs and fluorescence measurement, transcript profiling and RT-PCR.Results: For seven of eight C. albicans isolates tested, exposure to fluconazole gave an increase in Sap specific activity; for one isolate, resistant to azoles and flucytosine, fluconazole exposure led to a fall in Sap activity. A similar relationship between growth reduction and increased Sap activity was seen with C. albicans cells treated with subinhibitory concentrations of itraconazole, miconazole, flucytosine and caspofungin. Transcript profiling indicated antifungal exposure was associated with increased expression of mRNA from SAP2 and SAP9 genes; this was confirmed for fluconazole and caspofungin exposure by RT-PCR.Conclusions: Antifungal agents with three different mechanisms of action similarly generate a rise in expression of SAP2 and activity of the secreted Sap2 gene product, a known virulence factor, in most isolates of C. albicans. One isolate of the fungus showed an opposite response.

AB - Objectives: To ascertain the effects of subinhibitory concentrations of several antifungal agents on a virulence factor: secreted proteinase (Sap) activity and expression of SAP genes in Candida albicans.Methods: Enzyme assays and growth measurements, GFP-SAP2 promoter constructs and fluorescence measurement, transcript profiling and RT-PCR.Results: For seven of eight C. albicans isolates tested, exposure to fluconazole gave an increase in Sap specific activity; for one isolate, resistant to azoles and flucytosine, fluconazole exposure led to a fall in Sap activity. A similar relationship between growth reduction and increased Sap activity was seen with C. albicans cells treated with subinhibitory concentrations of itraconazole, miconazole, flucytosine and caspofungin. Transcript profiling indicated antifungal exposure was associated with increased expression of mRNA from SAP2 and SAP9 genes; this was confirmed for fluconazole and caspofungin exposure by RT-PCR.Conclusions: Antifungal agents with three different mechanisms of action similarly generate a rise in expression of SAP2 and activity of the secreted Sap2 gene product, a known virulence factor, in most isolates of C. albicans. One isolate of the fungus showed an opposite response.

KW - Antifungal Agents

KW - Aspartic Acid Endopeptidases

KW - Azoles

KW - Candida albicans

KW - Echinocandins

KW - Flucytosine

KW - Fungal Proteins

KW - Gene Expression Profiling

KW - Gene Expression Regulation, Fungal

KW - Green Fluorescent Proteins

KW - Humans

KW - Microbial Sensitivity Tests

KW - Oligonucleotide Array Sequence Analysis

KW - Peptides, Cyclic

KW - Recombinant Fusion Proteins

KW - Virulence Factors

KW - Fluconazole

KW - Caspofungin

KW - Itraconazole

KW - Amphotericin B

KW - Virulence genes

KW - Virulence

KW - Aspartyl Proteinases

KW - Subinhibitory concentrations

KW - In-vitro

KW - Adhesion

KW - Phagocytosis

KW - Macrophage

U2 - 10.1093/jac/dki088

DO - 10.1093/jac/dki088

M3 - Article

C2 - 15820985

SN - 0305-7453

VL - 55

SP - 645

EP - 654

JO - Journal of Antimicrobial Chemotherapy

JF - Journal of Antimicrobial Chemotherapy

IS - 5

ER -

Exposure of Candida albicans to antifungal agents affects expression of SAP2 and SAP9 secreted proteinase genes

Abstract

Keywords

Access to Document

Fingerprint

Cite this