Bojsen R~Regenberg B, 2013

Pubmed ID 23874964
Title The synthetic amphipathic peptidomimetic LTX109 is a potent fungicide that disturbs plasma membrane integrity in a sphingolipid dependent manner.
Authors Rasmus Bojsen, Rasmus Torbensen, Camilla Eggert Larsen, Anders Folkesson, Birgitte Regenberg
Abstract The peptidomimetic LTX109 (arginine-tertbutyl tryptophan-arginine-phenylethan) was previously shown to have antibacterial properties. Here, we investigated the activity of this novel antimicrobial peptidomimetic on the yeast Saccharomyces cerevisiae. We found that LTX109 was an efficient fungicide that killed all viable cells in an exponentially growing population as well as a large proportion of cells in biofilm formed on an abiotic surface. LTX109 had similar killing kinetics to the membrane-permeabilizing fungicide amphotericin B, which led us to investigate the ability of LTX109 to disrupt plasma membrane integrity. S. cerevisiae cells exposed to a high concentration of LTX109 showed rapid release of potassium and amino acids, suggesting that LTX109 acted by destabilizing the plasma membrane. This was supported by the finding that cells were permeable to the fluorescent nucleic acid stain SYTOX Green after a few minutes of LTX109 treatment. We screened a haploid S. cerevisiae gene deletion library for mutants resistant to LTX109 to uncover potential molecular targets. Eight genes conferred LTX109 resistance when deleted and six were involved in the sphingolipid biosynthetic pathway (SUR1, SUR2, SKN1, IPT1, FEN1 and ORM2). The involvement of all of these genes in the biosynthetic pathway for the fungal-specific lipids mannosylinositol phosphorylceramide (MIPC) and mannosyl di-(inositol phosphoryl) ceramide (M(IP)2C) suggested that these lipids were essential for LTX109 sensitivity. Our observations are consistent with a model in which LTX109 kills S. cerevisiae by nonspecific destabilization of the plasma membrane through direct or indirect interaction with the sphingolipids.
Citation PLoS One 2013; 8:e69483
Data abstract Deletion collection was screened for LTX109 resistance.

Datasets

Download the list of datasets
Paper Phenotype Condition Medium Collection Tested mutants Data Details
Bojsen R~Regenberg B, 2013 growth (spot assay) LTX109 [400 ug/ml] YPD hap a ~4,000 Discrete

Curation history

Tested strains

Aug. 6, 2020 To request.
Aug. 28, 2020 Not available.

Data

Aug. 6, 2020 Clarification needed.
Aug. 25, 2020 Request sent.
Aug. 28, 2020 Loaded.
Aug. 28, 2020 Ready to load.