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
Google Scholar
Right arrow Articles by Lis, M.
Right arrow Articles by Bobek, L. A.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lis, M.
Right arrow Articles by Bobek, L. A.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, September 2009, p. 3762-3769, Vol. 53, No. 9
0066-4804/09/$08.00+0     doi:10.1128/AAC.00668-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Exploring the Mode of Action of Antimicrobial Peptide MUC7 12-Mer by Fitness Profiling of Saccharomyces cerevisiae Genomewide Mutant Collection{triangledown}

Maciej Lis,* Jason R. Fuss, and Libuse A. Bobek

Department of Oral Biology, University at Buffalo, the State University of New York, Buffalo, New York 14214

Received 15 May 2009/ Returned for modification 13 June 2009/ Accepted 5 July 2009

The MUC7 12-mer (RKSYKCLHKRCR) is a cationic antimicrobial peptide derived from the human salivary mucin MUC7. To study its effect/mechanism of action on fungi, we performed a fitness screen of a tagged, diploid, homozygous gene deletion mutant pool of the yeast Saccharomyces cerevisiae grown in the presence of the MUC7 peptide. Forty-five strains exhibiting reduced fitness and 13 strains exhibiting increased fitness (sensitivity or resistance, respectively) were identified by hybridization intensities to tag arrays. The strongest fitness defects were observed with deletions in genes encoding elements of the RIM101 signaling pathway (regulating response to alkaline and neutral pH and other environmental conditions) and of the endosomal sorting complex required for transport (ESCRT; functioning mainly in protein sorting for degradation, but also required for activation of the RIM101 pathway). Other deletions identified as conferring fitness defect or gain are in genes associated with a variety of functions, including transcription regulation, protein trafficking, transport, metabolism, and others. The results of the pool fitness screen were validated by a set of mutant strains tested individually in the presence of the MUC7 12-mer. All tested RIM101-related deletion strains showing fitness defects confirmed their sensitivities. Taken together, the results led us to conclude that deletions of genes associated with the RIM101 pathway confer sensitivity to the peptide by preventing activation of this pathway and that this stress response plays a major role in the protection of S. cerevisiae against damage inflicted by the MUC7 12-mer peptide.

* Corresponding author. Mailing address: Department of Oral Biology, SUNY, Buffalo, 109 Foster Hall, 3435 Main Street, Buffalo, NY 14214-30932. Phone: (716) 829-6301. Fax: (716) 829-3942. E-mail: lis{at}buffalo.edu

{triangledown} Published ahead of print on 13 July 2009.

Antimicrobial Agents and Chemotherapy, September 2009, p. 3762-3769, Vol. 53, No. 9
0066-4804/09/$08.00+0     doi:10.1128/AAC.00668-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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