Analysis of a single-domain P-glycoprotein-like gene in the early-diverging protist Trichomonas vaginalis.
We have characterized a gene encoding an Adenosine triphosphate (ATP) Binding Cassette (ABC) transmembrane protein from Trichomonas vaginalis, an early-diverging protozoan parasite. This gene, Tvpgp1, encodes a 589-amino acid protein with an amino-terminal hydrophobic region, 6 potential membrane-spanning segments and a carboxy-terminal ATP binding site. Tvpgp1 is most similar in sequence to mammalian P-glycoproteins, 170 kDa transport proteins which are frequently overexpressed in multiple drug-resistant (Mdr) tumor cell lines. However, Tvpgp1 is half the size of typical P-glycoproteins which are tandem duplications. These data suggest that the duplication/fusion events which gave rise to the bipartite structure comprised of 2 similar halves which characterize eukaryotic P-glycoproteins may have occurred after the divergence of trichomonads (Parabasalia) from the main line of eukaryotic evolutionary descent. We have examined 7 metronidazole resistant strains of T. vaginalis to determine whether the Tvpgp1 gene is overexpressed or amplified. 2 drug resistant strains show a 2-3-fold overexpression and one shows a 20-fold overexpression of Tvpgp mRNA. The gene is not amplified in any of the drug resistant strains. On the contrary, 4 of the 7 resistant strains lack one of 2 Tvpgp genes found in drug-sensitive strains.
Johnson
P J
PJ
Department of Microbiology and Immunology, School of Medicine, University of California, Los Angeles 90024-1747.
Schuck
B L
BL
Delgadillo
M G
MG
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis / Q000235:genetics*; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics; D001483:Base Sequence; D003001:Cloning, Molecular; D016054:DNA, Protozoan / Q000032:analysis; D004351:Drug Resistance / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D017125:Genes, Protozoan / Q000235:genetics*; D008795:Metronidazole / Q000494:pharmacology; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000096:biosynthesis; D014246:Trichomonas vaginalis / Q000187:drug effects / Q000235:genetics*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018528:ATP-Binding Cassette Transporters; D001426:Bacterial Proteins; D016054:DNA, Protozoan; D012333:RNA, Messenger; D008795:Metronidazole