The antibiotic gentamicin inhibits specific protein trafficking functions of the arf1/2 family of GTPases

Lin Lin, Mark Wagner, Ross Cocklin, Alex Kuzma, Maureen Harrington, Bruce Molitoris, Mark Goebl

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Gentamicin is a highly efficacious antibiotic against Gram-negative bacteria. However, its usefulness in treating infections is compromised by its poorly understood renal toxicity. Toxic effects are also seen in a variety of other organisms. While the yeast Saccharomyces cerevisiae is relatively insensitive to gentamicin, mutations in any one of ∼20 genes cause a dramatic decrease in resistance. Many of these genes encode proteins important for translation termination or specific protein-trafficking complexes. Subsequent inspection of the physical and genetic interactions of the remaining gentamicin-sensitive mutants revealed a network centered on chitin synthase and the Arf GTPases. Further analysis has demonstrated that some conditional arf1 and gea1 alleles make cells hypersensitive to gentamicin under permissive conditions. These results suggest that one consequence of gentamicin exposure is disruption of Arfdependent protein trafficking.

Original languageEnglish
Pages (from-to)246-254
Number of pages9
JournalAntimicrobial Agents and Chemotherapy
Volume55
Issue number1
DOIs
StatePublished - Jan 2011

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GTP Phosphohydrolases
Protein Transport
Gentamicins
Anti-Bacterial Agents
Translational Peptide Chain Termination
Chitin Synthase
Poisons
Gram-Negative Bacteria
Saccharomyces cerevisiae
Yeasts
Alleles
Kidney
Mutation
Infection
Genes
Proteins

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology
  • Infectious Diseases

Cite this

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abstract = "Gentamicin is a highly efficacious antibiotic against Gram-negative bacteria. However, its usefulness in treating infections is compromised by its poorly understood renal toxicity. Toxic effects are also seen in a variety of other organisms. While the yeast Saccharomyces cerevisiae is relatively insensitive to gentamicin, mutations in any one of ∼20 genes cause a dramatic decrease in resistance. Many of these genes encode proteins important for translation termination or specific protein-trafficking complexes. Subsequent inspection of the physical and genetic interactions of the remaining gentamicin-sensitive mutants revealed a network centered on chitin synthase and the Arf GTPases. Further analysis has demonstrated that some conditional arf1 and gea1 alleles make cells hypersensitive to gentamicin under permissive conditions. These results suggest that one consequence of gentamicin exposure is disruption of Arfdependent protein trafficking.",
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AU - Wagner, Mark

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AU - Kuzma, Alex

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AU - Molitoris, Bruce

AU - Goebl, Mark

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