E. Bibi et al., FUNCTIONAL EXPRESSION OF MOUSE MDR1 IN ESCHERICHIA-COLI, Proceedings of the National Academy of Sciences of the United Statesof America, 90(19), 1993, pp. 9209-9213
We describe functional expression of the mouse multidrug-resistance pr
otein (P-glycoprotein; P-gp) in an Escherichia coli mutant defective i
n the outer membrane protease ompT. Heterologously expressed mdr1 appe
ars as an unglycosylated species with an apparent molecular mass of 14
0 kDa in the membrane of the mutant. Unglycosylated mdr1 retains the a
bility to bind the photoactivatable drug analog [I-125]iodoarylazidopr
azosin and confers resistance to tetraphenylphosphonium (TPP+) and tet
raphenylarsonium (TPA+), known mdr1 substrates. In vivo resistance is
linked to reduced cellular accumulation and energy-dependent efflux of
the lipophilic cations. Surprisingly, discrete mutations in the predi
cted nucleotide binding folds of mdr1 that abolish drug resistance in
mammalian cells have no apparent effect on TPA+ efflux via mdr1 in E.
coli.