| Title: |
The polyene antifungals, amphotericin B and nystatin, cause cell death in Saccharomyces cerevisiae by a distinct mechanism to amphibian-derived antimicrobial peptides |
| Authors: |
Serhan, George (S32052); Stack, Colin M. (R12090); Perrone, Gabriel G. (R16702); Morton, Charles O. (R16967) |
| Contributors: |
School of Science and Health (Host institution) |
| Publisher Information: |
U.K., BioMed Central |
| Publication Year: |
2014 |
| Collection: |
University of Western Sydney (UWS): Research Direct |
| Subject Terms: |
060505 - Mycology; 920109 - Infectious Diseases |
| Description: |
Background: There is a pressing need to identify novel antifungal drug targets to aid in the therapy of life-threatening mycoses and overcome increasing drug resistance. Identifying specific mechanisms of action of membrane-interacting antimicrobial drugs on the model fungus Saccharomyces cerevisiae is one avenue towards addressing this issue. The S. cerevisiae deletion mutants Deltaizh2, Deltaizh3, Deltaaif1 and Deltastm1 were demonstrated to be resistant to amphibian-derived antimicrobial peptides (AMPs). The purpose of this study was to examine whether AMPs and polyene antifungals have a similar mode of action; this was done by comparing the relative tolerance of the mutants listed above to both classes of antifungal. Findings: In support of previous findings on solid media it was shown that Deltaizh2 and Deltaizh3 mutants had increased resistance to both amphotericin B (1-2 mug ml-1) and nystatin (2.5 - 5 mug ml-1) in liquid culture, after acute exposure. However, Deltaaif1 and Deltastm1 had wild-type levels of susceptibility to these polyenes. The generation of reactive oxygen species (ROS) after exposure to amphotericin B was also reduced in Deltaizh2 and Deltaizh3. These data indicated that polyene antifungal and AMPs may act via distinct mechanisms of inducing cell death in S. cerevisiae. Conclusions: Further understanding of the mechanism(s) involved in causing cell death and the roles of IZH2 and IZH3 in drug susceptibility may help to inform improved drug design and treatment of fungal pathogens. |
| Document Type: |
article in journal/newspaper |
| File Description: |
print |
| Language: |
English |
| Relation: |
Annals of Clinical Microbiology and Antimicrobials--1476-0711 Vol. 13 Issue. 18 |
| DOI: |
10.1186/1476-0711-13-18 |
| Availability: |
http://handle.uws.edu.au:8081/1959.7/542894; https://doi.org/10.1186/1476-0711-13-18 |
| Rights: |
© 2014 Serhan et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
| Accession Number: |
edsbas.4FFE1FFF |
| Database: |
BASE |