in the efg1 mutant is associated with attenuated virulence during infection of oral epithelium

Robert Koch-Institut, Berlin, GermanyThe transition of Candida albicans from a yeast to a hyphal form is controlled by severaltranscriptionalfactors,includingthekeyregulatorsCph1andEfg1,andisconsideredanimportantvirulence attribute. These factors, especially Efg1, regulate the expression of hyphal-associatedgenese.g.SAP4–SAP6.Inordertoinvestigatetherelevanceofthesetranscriptionalregulatorsforhyphal-independent SAP genes, recently constructed cph1 and efg1 single mutants and a cph1/efg1 double mutant lacking these factors were tested during interaction with oral epithelium andpolymorphonuclearneutrophils.Incontrasttotheparentalwild-typestrainandthecph1mutant,theefg1 and the cph1/efg1 mutants did not produce hyphal forms in all experiments and were lesscapableofdamagingepithelialcellsandneutrophilgranulocytes.Theattenuatedepitheliallesionsofthese mutants were correlated not only with reduced expression of the hyphal-associated geneSAP4,butalsowiththelackofSAP1andSAP3expressionpreviouslyshowntobeimportantfororalinfections. An efg1mutant strain carrying a plasmid-borne copyof the EFG1 generegained hyphalgrowth, damage of keratinocytes, granulocytes and the expression of SAP1 and SAP3. Althoughefg1andcph1/efg1mutantsdidnotproducegermtubesduringinfection,expressionofthehyphal-associatedgenesSAP5andSAP6wasnotcompletelyabolished.AreducedcapacitytostimulateanepithelialimmuneresponsemanifestedbyadelayedonsetofIL-1 ,IL-8andTNFexpressionwasonly observed in the cph1/efg1-infected tissue. These results provide further evidence for acombined regulation of different virulence factors, such as dimorphism and expression of SAPgenes.Furthermore,itcouldbedemonstratedthatthelackofEfg1alsocausedreducedexpressionofhyphal-independentSAPgenes.BoththeEFG1andtheCPH1geneproductsarenecessaryforadequate induction of an immune response.