Preparing your results

Our searching services are busy right now. Your search will reload in five seconds.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Fungicidal drugs induce a common oxidative-damage cellular death pathway.

Cell reports | Feb 21, 2013

http://www.ncbi.nlm.nih.gov/pubmed/23416050

Amphotericin, miconazole, and ciclopirox are antifungal agents from three different drug classes that can effectively kill planktonic yeast, yet their complete fungicidal mechanisms are not fully understood. Here, we employ a systems biology approach to identify a common oxidative-damage cellular death pathway triggered by these representative fungicides in Candida albicans and Saccharomyces cerevisiae. This mechanism utilizes a signaling cascade involving the GTPases Ras1 and Ras2 and protein kinase A, and it culminates in death through the production of toxic reactive oxygen species in a tricarboxylic-acid-cycle- and respiratory-chain-dependent manner. We also show that the metabolome of C. albicans is altered by antifungal drug treatment, exhibiting a shift from fermentation to respiration, a jump in the AMP/ATP ratio, and elevated production of sugars; this coincides with elevated mitochondrial activity. Lastly, we demonstrate that DNA damage plays a critical role in antifungal-induced cellular death and that blocking DNA-repair mechanisms potentiates fungicidal activity.

Pubmed ID: 23416050 RIS Download

Mesh terms: Amphotericin B | Antifungal Agents | Candida albicans | Citric Acid Cycle | Cyclic AMP-Dependent Protein Kinases | DNA Damage | Electron Transport | Fungal Proteins | Metabolome | Miconazole | Mitochondria | Pyridones | Reactive Oxygen Species | Saccharomyces cerevisiae | Saccharomyces cerevisiae Proteins | ras Proteins

Research resources used in this publication

None found

Research tools detected in this publication

None found

Data used in this publication

None found

Associated grants

  • Agency: NIH HHS, Id: DP1 OD003644
  • Agency: NIH HHS, Id: DP1 OD003644
  • Agency: Howard Hughes Medical Institute, Id:

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.