A single chemical, identified as bithionol, strongly inhibited the growth of the ρ 0 but inhibited the growth of wild type yeast very weakly (Figure 1C). Since antimycin A directly blocks the mitochondrial electron-transfer chain, a difference in drug response between wild

type and ρ 0 strains was to be expected and this compound was not studied further. Figure 1 Halo screen of chemical collection with ρ + and ρ 0 FY1679-28C/TDEC. (A) Suloctidil and myriocin selectively inhibit growth of ρ + cells; (B) Antimycin A selectively Deforolimus slows growth of ρ +; (C) Increased sensitivity of ρ 0 cells to bithionol. Table 1 51 growth-inhibitory compounds identified in halo toxiCity screen Compound ρ buy Target Selective Inhibitor Library + ρ 0 Antibiotics and antiseptics        Antimycin A ++ –    Cefoperazone sodium ++ ++    Cetylpyridinium chloride + +    Chloroxine + +    Hexachlorophene ++ ++    Myriocin ++ –    Thimerosal ++ ++    Tunicamycin

B ++ ++ Anticancer        Swainsonine ++ ++    Dequalinium analog C-14 linker + +    dhMotC ++ – Azoles        Bifonazole ++ ++    Butoconazole nitrate +++ +++    Clotrimazole +++ +++    Econazole nitrate +++ +++    Enilconazole ++ ++    Isoconazole +++ +++    Ketoconazole ++ ++    Miconazole +++ +++    Miconazole nitrate +++ +++    Oxiconazole nitrate +++ +++    Sertaconazole nitrate +++ +++    Sulconazole nitrate +++ +++ Detergents        Cetrimonium bromide + +    Digitonin + + Flavonoids        Luteolin ++ ++ Other        Adamantamine fumarate ++ ++    Amiodarone hydrochloride + +    Anthothecol + +    Benzalkonium chloride + +    Bithionol + +++    Cedrelone + +    Celastrol + +    Dequalinium dichloride ++ ++    Elaidylphosphocholine + +    Ellagic acid + +    Gentian violet ++ ++    Miltefosine + +    Obtusaquinone + Gemcitabine clinical trial +    Phenylmercuric acetate +++ +++    Phytosphingosine + +    Plumbagin + +    Pyrithione zinc ++ ++    Pyrvinium pamoate + +    Rapamycin +++ +++    Shikonin + +    SKF96365 ++ ++    Suloctidil ++ –    Thiram + +    Tomatidine hydrochloride + +    Totarol + + Comparison between respiratory-proficient and -deficient yeast strains. The results of the halo screen were

confirmed and extended using a quantitative liquid growth assay. Suloctidil (50 μM), myriocin (0.25 μM) and dhMotC (60 μM) all inhibited the growth of the wild type strain while ρ 0 cells were resistant (Table 2). P 0 strains have previously been shown to have increased expression of multidrug resistance genes [17], which could have explained their increased resistance to the 4 chemicals. However, this is not the case since increased resistance was also observed in the ρ 0 strain lacking PDR1 and PDR3, that cannot express multidrug resistance genes, in agar (Table 1), as well as in liquid assay (data not shown). Therefore, resistance to the growth inhibitory effect of the chemicals is due to the lack of mitochondrial function.