Thomas Edlind

..These data provide a framework for understanding 5FC resistance in C. glabrata and potentially in other fungal pathogens...

..Using this PDR5 promoter-URA3 recombinant, we further demonstrate a simple extension of the method that yields regulatory mutants via 5-fluoroorotic acid selection. PRODIGE warrants testing in other yeast, molds, and beyond...

..Our results implicate cAMP signaling in the yeast azole response; compounds similar to MDL-12330A may be useful adjuvants in azole therapy...

..glabrata confirmed its role in RES. Y641-equivalent Fks residues were identified in intrinsically RES Fusarium species and Candida guilliermondii...

..cerevisiae with azole or terbinafine resulted in transcriptional upregulation of genes FKS2 and PMR1 known to be Ca2+ regulated. A model to explain the role of Ca2+-regulated signalling in azole/terbinafine tolerance is proposed...

..Additional regulatory factors remain to be identified, as indicated by the lack of PDR1 mutation in a clinical isolate with coordinately upregulated CDR1-PDH1...

..cerevisiae and 8- to 32-fold less than that of the same hybrid with an F639 mutation. We propose that Fks1 sequences represent determinants of intrinsic EC resistance in Fusarium and Scedosporium species and, potentially, other fungi...

..Fks1 sequences from intrinsically RES Scedosporium species revealed W695F-equivalent substitutions; Fks1 hybrids expressing Scedosporium prolificans hot spot 3 confirmed that this substitution imparts RES...

..CRS-MIS mutants were generated from all 10 C. glabrata strains tested and were tentatively identified within a collection of clinical isolates. Intriguingly, sequencing and gene disruption demonstrated that CRS-MIS is Fks independent...

..C. glabrata provides a promising model for studying the genetic basis of multidrug resistance and its impact on virulence...

..MICs were unchanged, and trailing growth generally decreased. With CPC-fluconazole combinations, both antagonism and synergism were observed, which can be explained, in part, by CDR1-CDR2 multidrug transporter upregulation...

..These inverse correlations suggest that transcriptional regulation of ROX1 is an important determinant of ERG expression and hence of azole and terbinafine susceptibilities...

..This most likely explains the inhibition of azole and terbinafine trailing by TSA and, more generally, provides evidence that trailing is mediated by upregulation of target enzymes and multidrug transporters...

..In contrast, fungicidal activity and no chitin increase were observed in an isogenic Delta slt2 strain, suggesting a role for SLT2 and chitin production in the response of C. glabrata to caspofungin...

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..glabrata Pdr1, "master regulator" of azole resistance;they will confer a deep understanding of the molecular basis for azole resistance, and could lead to novel strategies to prevent or reverse resistance. ..

..These studies will accelerate the development of second generation ECs that provide a broader spectrum of protection from fungal pathogens. ..

..glabrata Pdr1, "master regulator" of azole resistance; they will confer a deep understanding of the molecular basis for azole resistance, and could lead to novel strategies to prevent or reverse resistance. ..

..Finally, the signalling pathway responsible for azole-dependent upregulation of ERG expression will be elucidated with a focus on Rox1p and Haplp transcription factors. ..

..Candida homologues of these factors will be identified by PCR or expression in S. cerevisiae. Their role in MDR induction will be examined by gene disruption. ..

..These studies will accelerate the development of second generation ECs that provide a broader spectrum of protection from fungal pathogens. ..