Heterologously expressed bacterial and human multidrug resistance proteins confer cadmium resistance to Escherichia coli.
The human MDR1 gene is induced by cadmium exposure although no resistance to this metal is observed in human cells overexpressing hMDR1. To access the role of MDR proteins in cadmium resistance, human MDR1, Lactococcus lactis lmrA, and Oenococcus oeni omrA were expressed in an Escherichia coli tolC mutant strain which proved to be hypersensitive to cadmium. Both the human and bacterial MDR genes conferred cadmium resistance to E. coli up to 0.4 mM concentration. Protection was abolished by 100 microM verapamil. Quantification of intracellular cadmium concentration by atomic absorption spectrometry showed a reduced cadmium accumulation in cells expressing the MDR genes. Inside-out membrane vesicles of L. lactis overexpressing lmrA displayed an ATP-dependent (109)Cd(2+) uptake that was stimulated by glutathione. An evolutionary model is discussed in which MDR proteins have evolved independently from an ancestor protein displaying both organic xenobiotic- and divalent metal-extrusion abilities.
Achard-Joris
Maud
M
Laboratoire d'Ecophysiologie et d'Ecotoxicologie des Systèmes Aquatiques, Université Bordeaux 1/UMR CNRS 5805, Place du Dr. Peyneau, 33120 Arcachon, France.
van den Berg van Saparoea
H Bart
HB
Driessen
Arnold J M
AJ
Bourdineaud
Jean-Paul
JP
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism / Q000633:toxicity; D018432:Drug Resistance, Multiple / Q000235:genetics; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D005798:Genes, Bacterial; D006801:Humans; D066298:In Vitro Techniques; D013294:Lactococcus lactis / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D001426:Bacterial Proteins; D002118:Calcium; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D011994:Recombinant Proteins; C101824:LmrA protein, Lactococcus lactis