Molecular basis for resistance of acanthamoeba tubulins to all major classes of antitubulin compounds.
Tubulin is essential to eukaryotic cells and is targeted by several antineoplastics, herbicides, and antimicrobials. We demonstrate that Acanthamoeba spp. are resistant to five antimicrotubule compounds, unlike any other eukaryote studied so far. Resistance correlates with critical amino acid differences within the inhibitor binding sites of the tubulin heterodimers.
Henriquez
Fiona L
FL
Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 27 Taylor Street, Glasgow G4 0NR, United Kingdom. fiona.henriquez@paisley.ac.uk
Ingram
Paul R
PR
Muench
Stephen P
SP
Rice
David W
DW
Roberts
Craig W
CW
D000048:Acanthamoeba / Q000145:classification / Q000187:drug effects* / Q000235:genetics; D048248:Acanthamoeba castellanii / Q000187:drug effects / Q000235:genetics; D015766:Albendazole / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites / Q000235:genetics*; D003078:Colchicine / Q000494:pharmacology; D004136:Dinitrobenzenes / Q000494:pharmacology; D004351:Drug Resistance / Q000235:genetics*; D008958:Models, Molecular; D017239:Paclitaxel / Q000494:pharmacology; D021261:Parasitic Sensitivity Tests / Q000379:methods; D013424:Sulfanilamides / Q000494:pharmacology; D014404:Tubulin / Q000737:chemistry* / Q000235:genetics*; D050257:Tubulin Modulators / Q000494:pharmacology*; D014747:Vinblastine / Q000494:pharmacology
D004136:Dinitrobenzenes; D013424:Sulfanilamides; D014404:Tubulin; D050257:Tubulin Modulators; D014747:Vinblastine; C012465:oryzalin; D015766:Albendazole; D017239:Paclitaxel; D003078:Colchicine