Exposure of Candida albicans to antifungal agents affects expression of SAP2 and SAP9 secreted proteinase genes.
OBJECTIVE
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.
Copping
Vanessa M S
VM
Aberdeen Fungal Group, School of Medical Sciences, University of Aberdeen, Aberdeen AB25 2ZD, UK.
Barelle
Caroline J
CJ
Hube
Bernhard
B
Gow
Neil A R
NA
Brown
Alistair J P
AJ
Odds
Frank C
FC
D000935:Antifungal Agents / Q000494:pharmacology*; D016282:Aspartic Acid Endopeptidases / Q000235:genetics / Q000378:metabolism*; D001393:Azoles / Q000494:pharmacology; D002176:Candida albicans / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics / Q000472:pathogenicity; D000077336:Caspofungin; D054714:Echinocandins; D005437:Flucytosine / Q000494:pharmacology; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D015966:Gene Expression Regulation, Fungal; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D055666:Lipopeptides; D008826:Microbial Sensitivity Tests; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D010456:Peptides, Cyclic / Q000494:pharmacology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism
D000935:Antifungal Agents; D001393:Azoles; D054714:Echinocandins; D005656:Fungal Proteins; D055666:Lipopeptides; D010456:Peptides, Cyclic; D011993:Recombinant Fusion Proteins; D037521:Virulence Factors; D049452:Green Fluorescent Proteins; D005437:Flucytosine; D016282:Aspartic Acid Endopeptidases; C090753:SAP2 protein, Candida; C116371:Sap9 protein, Candida albicans; D000077336:Caspofungin