f Identification of an overexpressed yeast gene which prevents aminoglycoside toxicity
- Authors: Toni R. Prezant, William E.jr Chaltraw, Nathan Fischel-Ghodsian
- Author for correspondence: Toni R. Prezant. Tel: +1 310 855 4984. Fax: +1 310 659 9125. e-mail: tPrezant@mailgate.csmc.edu
- Microbiology, December 1996 142: 3407-3414, doi: 10.1099/13500872-142-12-3407
- Subject: Genetics And Molecular Biology
- Published Online:
Summary: Aminoglycoside antibiotics, used to treat bacterial infections by interfering with proofreading during protein synthesis, cause sensorineural hearing loss in genetically susceptible individuals. The only aminoglycoside-hypersensitivity mutations which have been described in humans are in the mitochondrial 12S rRNA gene, potentially allowing increased antibiotic binding to mitochondrial ribosomes. To identify additional predisposing mutations, a yeast model system was used to isolate genes which interact with or bypass the effects of aminoglycoside antibiotics. A novel yeast gene was isolated which, in high copy, confers neomycin resistance to yeast transformants. The neomycin-resistance 1 gene (NEO1) encodes a potential 1151 aa integral membrane protein, most homologous to the yeast DRS2 gene product, a Ca2+-ATPase involved in cytoplasmic ribosome assembly. The N-terminus of Neo1p is partially homologous to abrin A-chain, another protein which interacts with cytoplasmic ribosomes. Mutagenesis experiments demonstrate that the NEO1 product is essential for vegetative growth and that the drug-resistance phenotype requires ATPase function.
- Keyword(s): overexpression, Keywords: aminoglycoside, toxicity, cation ATPase, Saccharomyces cerevisiae
© Society for General Microbiology 1996 | Published by the Microbiology Society
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