Hsp21 potentiates antifungal drug tolerance in Candida albicans

PLoS One. 2013;8(3):e60417. doi: 10.1371/journal.pone.0060417. Epub 2013 Mar 22.

Abstract

Systemic infections of humans with the fungal pathogen Candida albicans are associated with a high mortality rate. Currently, efficient treatment of these infections is hampered by the relatively low number of available antifungal drugs. We recently identified the small heat shock protein Hsp21 in C. albicans and demonstrated its fundamental role for environmental stress adaptation and fungal virulence. Hsp21 was found in several pathogenic Candida species but not in humans. This prompted us to investigate the effects of a broad range of different antifungal drugs on an Hsp21-null C. albicans mutant strain. Our results indicate that combinatorial therapy targeting Hsp21, together with specific antifungal drug targets, has strong synergistic potential. In addition, we demonstrate that Hsp21 is required for tolerance to ethanol-induced stress and induction of filamentation in response to pharmacological inhibition of Hsp90. These findings might pave the way for the development of new treatment strategies against Candida infections.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amphotericin B / pharmacology
  • Antifungal Agents / pharmacology*
  • Candida albicans / drug effects*
  • Candida albicans / metabolism*
  • Drug Resistance, Fungal / genetics
  • Drug Resistance, Fungal / physiology
  • Fungal Proteins / chemistry
  • Fungal Proteins / classification
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism*
  • HSP90 Heat-Shock Proteins / chemistry
  • HSP90 Heat-Shock Proteins / genetics
  • HSP90 Heat-Shock Proteins / metabolism
  • Heat-Shock Proteins / chemistry
  • Heat-Shock Proteins / classification
  • Heat-Shock Proteins / genetics
  • Heat-Shock Proteins / metabolism*
  • Humans
  • Phylogeny

Substances

  • Antifungal Agents
  • Fungal Proteins
  • HSP90 Heat-Shock Proteins
  • Heat-Shock Proteins
  • Amphotericin B

Grant support

FLM and BH were supported by the International Leibniz Research School for Microbial and Biomolecular Interactions (ILRS) as part of the excellence graduate school Jena School for Microbial Communication (JSMC). DW and BH were supported by the ERA-NET PathoGenoMics Program (Candicol; BMBF 0315 901 B). BH was also funded by the European Commission through the FINSysB Marie Curie Initial Training Network (PITN-GA-2008-214004), by the Center for Sepsis Control and Care (CSCC; BMBF 01EO1002), and by the Deutsche Forschungsgemeinschaft (DFG Hu 528/15, 16 and 17). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.