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

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4 Scopus citations

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 (US)
Pages (from-to)246-254
Number of pages9
JournalAntimicrobial Agents and Chemotherapy
Volume55
Issue number1
DOIs
StatePublished - Jan 1 2011

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

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