R. Kaur et Ak. Bachhawat, The yeast multidrug resistance pump, Pdr5p, confers reduced drug resistance in erg mutants of Saccharomyces cerevisiae, MICROBIO-UK, 145, 1999, pp. 809-818
Mutants of Saccharomyces cerevisiae bearing lesions in the ergosterol biosy
nthetic pathway exhibit a pleiotropic drug-sensitive phenotype. This has be
en reported to result from an increased permeability of the membranes of th
e mutant strains to different drugs. As disruption of the yeast multidrug r
esistance protein, Pdr5p, results in a similar pleiotropic drug-sensitive p
henotype, the possibility that Pdr5p may be functioning with a reduced effi
ciency in these altered sterol backgrounds was examined. To do this, the fu
nction of Pdr5p in isogenic strains of S. cerevisiae that have disruptions
in the late stages of the ergosterol biosynthesis pathway (ERG6, ERG2, ERG3
, ERG4) was studied. A reduced ability of Pdr5p to confer resistance to dif
ferent drugs in these strains was observed, which did not appear to be depe
ndent solely on the permeability of the membrane towards the drug. A simult
aneous examination was made of how the lipid composition might be altering
the efficiency of Pdr5p by similar studies in strains lacking phosphatidyls
erine synthase (encoded by CHO1). The results indicated that the drug sensi
tivity of the erg strains is, to a significant extent, a result of the redu
ced efficiency of the Pdr5p efflux pump, and that the membrane environment
plays an important role in determining the drug resistance conferred by Pdr
5p.