Lis M~Bobek LA, 2013

Pubmed ID 23208710
Title Chemical genomic screening of a Saccharomyces cerevisiae genomewide mutant collection reveals genes required for defense against four antimicrobial peptides derived from proteins found in human saliva.
Authors Maciej Lis, Sanjay Bhatt, Nathan E Schoenly, Anna Y Lee, Corey Nislow, Libuse A Bobek
Abstract To compare the effects of four antimicrobial peptides (MUC7 12-mer, histatin 12-mer, cathelicidin KR20, and a peptide containing lactoferricin amino acids 1 to 11) on the yeast Saccharomyces cerevisiae, we employed a genomewide fitness screen of combined collections of mutants with homozygous deletions of nonessential genes and heterozygous deletions of essential genes. When an arbitrary fitness score cutoffs of 1 (indicating a fitness defect, or hypersensitivity) and -1 (indicating a fitness gain, or resistance) was used, 425 of the 5,902 mutants tested exhibited altered fitness when treated with at least one peptide. Functional analysis of the 425 strains revealed enrichment among the identified deletions in gene groups associated with the Gene Ontology (GO) terms "ribosomal subunit," "ribosome biogenesis," "protein glycosylation," "vacuolar transport," "Golgi vesicle transport," "negative regulation of transcription," and others. Fitness profiles of all four tested peptides were highly similar, particularly among mutant strains exhibiting the greatest fitness defects. The latter group included deletions in several genes involved in induction of the RIM101 signaling pathway, including several components of the ESCRT sorting machinery. The RIM101 signaling regulates response of yeasts to alkaline and neutral pH and high salts, and our data indicate that this pathway also plays a prominent role in regulating protective measures against all four tested peptides. In summary, the results of the chemical genomic screens of S. cerevisiae mutant collection suggest that the four antimicrobial peptides, despite their differences in structure and physical properties, share many interactions with S. cerevisiae cells and consequently a high degree of similarity between their modes of action.
Citation Antimicrob. Agents Chemother. 2013; 57:840-7

Datasets

Download the list of datasets
Paper Phenotype Condition Medium Collection Tested mutants Data Details
Lis M~Bobek LA, 2013 growth (relative abundance in pooled culture) MUC7 peptide [10 uM] hom 4,872 Quantitative
Lis M~Bobek LA, 2013 growth (relative abundance in pooled culture) histatin 12-mer [20 uM] hom 4,872 Quantitative
Lis M~Bobek LA, 2013 growth (relative abundance in pooled culture) cathelicidin KR20 [10 uM] hom 4,872 Quantitative
Lis M~Bobek LA, 2013 growth (relative abundance in pooled culture) lactoferricin aa 1-11 [12 uM] hom 4,872 Quantitative
Lis M~Bobek LA, 2013 growth (relative abundance in pooled culture) MUC7 peptide [10 uM] het 1,030 Quantitative
Lis M~Bobek LA, 2013 growth (relative abundance in pooled culture) histatin 12-mer [20 uM] het 1,030 Quantitative
Lis M~Bobek LA, 2013 growth (relative abundance in pooled culture) cathelicidin KR20 [10 uM] het 1,030 Quantitative
Lis M~Bobek LA, 2013 growth (relative abundance in pooled culture) lactoferricin aa 1-11 [12 uM] het 1,030 Quantitative

Curation history

Data

March 31, 2016 Loaded.

Tested strains

March 31, 2016 Loaded.