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Cellular conditions that modulate the fungicidal activity of occidiofungin

C A Robinson1, C Denison1, A Burkenstock1

  • 1Department of Biological Sciences, Mississippi State University, Mississippi State, MS, USA.

Journal of Applied Microbiology
|May 31, 2017
PubMed
Abstract

Insights

High extracellular calcium and magnesium levels confer resistance to the antimicrobial peptide occidiofungin in yeast. Quiescent yeast cells also show resistance, indicating active growth is necessary for occidiofungin

Area of Science:

  • Microbiology
  • Mycology
  • Antimicrobial Research

Background:

  • Antimicrobial peptides (AMPs) are crucial in fighting fungal infections.
  • Occidiofungin is a novel AMP with demonstrated antifungal activity.
  • Understanding factors influencing AMP efficacy is vital for developing new antifungal strategies.

Purpose of the Study:

  • To investigate cellular conditions affecting the susceptibility of Saccharomyces cerevisiae, Candida albicans, and Candida glabrata to occidiofungin.
  • To elucidate the role of calcium signaling in occidiofungin resistance.
  • To determine if cell quiescence impacts occidiofungin activity.

Main Methods:

  • Utilized genetic and pharmacological approaches to study occidiofungin susceptibility.
  • Employed Minimum Inhibitory Concentration (MIC) and drop assays.
  • Conducted short-term time-kill assays.

Main Results:

  • Extracellular calcium and magnesium ions significantly increased resistance to occidiofungin (fourfold resistance with calcium).
  • This calcium-mediated resistance was independent of the calmodulin-calcineurin pathway.
  • Occidiofungin was ineffective against quiescent yeast cells, as well as cells exposed to cycloheximide or depleted media.

Conclusions:

  • Extracellular calcium confers fungal tolerance to occidiofungin, bypassing the calmodulin-calcineurin pathway.
  • Active cellular growth is essential for occidiofungin's mechanism of action, as evidenced by resistance in quiescent cells.
  • Identifying these cellular conditions provides insights into occidiofungin's targets and potential applications against fungal pathogens.
Keywords:
antifungalcalcium signallingfungiquiescenceresistance

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