This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Blackburn, A. S.
Right arrow Articles by Avery, S. V.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Blackburn, A. S.
Right arrow Articles by Avery, S. V.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, February 2003, p. 676-681, Vol. 47, No. 2
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.2.676-681.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Genome-Wide Screening of Saccharomyces cerevisiae To Identify Genes Required for Antibiotic Insusceptibility of Eukaryotes

Alexandra S. Blackburn and Simon V. Avery*

School of Life and Environmental Sciences, University of Nottingham, University Park, Nottingham NG7 2RD, United Kingdom

Received 5 July 2002/ Returned for modification 15 October 2002/ Accepted 12 November 2002

The adverse reactions provoked by many antibiotics in humans are well documented but are generally poorly understood at the molecular level. To elucidate potential genetic defects that could give rise to susceptibility to prokaryote-specific antibiotics in eukaryotes, we undertook genome-wide screens using the yeast Saccharomyces cerevisiae as a model of eukaryotes; our previous work with a small number of yeast mutants revealed some specific gene functions required for oxytetracycline resistance. Here, the complete yeast deletion strain collection was tested for growth in the presence of a range of antibiotics. The sensitivities of mutants revealed by these screens were validated in independent tests. None of the ~4,800 defined deletion strains tested were found to be sensitive to amoxicillin, penicillin G, rifampin, or vancomycin. However, two of the yeast mutants were tetracycline sensitive and four were oxytetracycline sensitive; encompassed among the latter were mutants carrying deletions in the same genes that we had characterized previously. Seventeen deletion strains were found to exhibit growth defects in the presence of gentamicin, with MICs for the strains being as low as 32 µg ml-1 (the wild type exhibited no growth defects at any gentamicin concentration tested up to 512 µg ml-1). Strikingly, 11 of the strains that were most sensitive to gentamicin carried deletions in genes whose products are all involved in various aspects of vacuolar and Golgi complex (or endoplasmic reticulum) function. Therefore, these and analogous organelles, which are also the principal sites of gentamicin localization in human cells, appear to be essential for normal resistance to gentamicin in eukaryotes. The approach and data described here offer a new route to gaining insight into the potential genetic bases of antibiotic insusceptibilities in eukaryotes.

* Corresponding author. Mailing address: School of Life and Environmental Sciences, University of Nottingham, University Park, Nottingham NG7 2RD, United Kingdom. Phone: 44-115-9513315. Fax: 44-115-9513251. E-mail: Simon.Avery{at}nottingham.ac.uk.

Antimicrobial Agents and Chemotherapy, February 2003, p. 676-681, Vol. 47, No. 2
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.2.676-681.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Khozoie, C., Pleass, R. J., Avery, S. V. (2009). The Antimalarial Drug Quinine Disrupts Tat2p-mediated Tryptophan Transport and Causes Tryptophan Starvation. J. Biol. Chem. 284: 17968-17974 [Abstract] [Full Text]  
  • Chamilos, G., Lewis, R. E., Lamaris, G. A., Albert, N. D., Kontoyiannis, D. P. (2008). Genomewide Screening for Genes Associated with Gliotoxin Resistance and Sensitivity in Saccharomyces cerevisiae. Antimicrob. Agents Chemother. 52: 1325-1329 [Abstract] [Full Text]  
  • Wagner, M. C., Molnar, E. E., Molitoris, B. A., Goebl, M. G. (2006). Loss of the Homotypic Fusion and Vacuole Protein Sorting or Golgi-Associated Retrograde Protein Vesicle Tethering Complexes Results in Gentamicin Sensitivity in the Yeast Saccharomyces cerevisiae. Antimicrob. Agents Chemother. 50: 587-595 [Abstract] [Full Text]  
  • Markovich, S., Yekutiel, A., Shalit, I., Shadkchan, Y., Osherov, N. (2004). Genomic Approach to Identification of Mutations Affecting Caspofungin Susceptibility in Saccharomyces cerevisiae. Antimicrob. Agents Chemother. 48: 3871-3876 [Abstract] [Full Text]  
  • Avery, A. M., Goddard, H. J., Sumner, E. R., Avery, S. V. (2004). Iron Blocks the Accumulation and Activity of Tetracyclines in Bacteria. Antimicrob. Agents Chemother. 48: 1892-1894 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»