Disease relevance of PDH1

• Here we show that disruption of C. glabrata PDR1 conferred equivalent fluconazole hypersensitivity (MIC = 2 microg ml(-1)) to both F15 and 66032 and eliminated both constitutive and fluconazole-induced CDR1-PDH1 expression [1].

High impact information on PDH1

• Rephosphorylation of Pdh1p and Cdr1p was protein kinase A inhibitor-sensitive but responded differentially to Tpk isoforms, stressors, and glucose concentration [2].
• This suggests that phosphorylation of Pdh1p may be required for efficient coupling of NTPase activity with drug efflux [3].
• In 4 of these 10 isolates PDH1 was similarly upregulated, and in the remainder it was upregulated three- to fivefold, while ERG11 expression was minimally changed [4].
• Fluconazole resistance associated with drug efflux and increased transcription of a drug transporter gene, PDH1, in Candida glabrata [5].
• PDH1, CgCDR1 and PDR5 have striking similarities in function and regulation [6].

Biological context of PDH1

• Expression of PDH1 in a C. glabrata cgcdr1::ura3 pdh1Delta::ura3 mutant using a multicopy plasmid almost completely restored the wild-type phenotype, showing that PDH1 at higher levels of expression can replace CgCDR1 [6].

Associations of PDH1 with chemical compounds

• Abundance of PDH1 and CgCDR1 mRNA in C. glabrata was increased by rhodamine 6G, cycloheximide and oligomycin, properties in common with PDR5 [6].
• Disruption of PDH1 in a cgcdr1::ura3 strain increased susceptibility to rhodamine 6G, cycloheximide and chloramphenicol, and also increased rhodamine 6G accumulation, all properties of pdr5 null mutants [6].

References