Metabolic response of Candida albicans to phenylethyl alcohol under hyphae-inducing conditions

PLoS One. 2013 Aug 12;8(8):e71364. doi: 10.1371/journal.pone.0071364. eCollection 2013.

Abstract

Phenylethyl alcohol was one of the first quorum sensing molecules (QSMs) identified in C. albicans. This extracellular signalling molecule inhibits the hyphal formation of C. albicans at high cell density. Little is known, however, about the underlying mechanisms by which this QSM regulates the morphological switches of C. albicans. Therefore, we have applied metabolomics and isotope labelling experiments to investigate the metabolic changes that occur in C. albicans in response to phenylethyl alcohol under defined hyphae-inducing conditions. Our results showed a global upregulation of central carbon metabolism when hyphal development was suppressed by phenylethyl alcohol. By comparing the metabolic changes in response to phenylethyl alcohol to our previous metabolomic studies, we were able to short-list 7 metabolic pathways from central carbon metabolism that appear to be associated with C. albicans morphogenesis. Furthermore, isotope-labelling data showed that phenylethyl alcohol is indeed taken up and catabolised by yeast cells. Isotope-labelled carbon atoms were found in the majority of amino acids as well as in lactate and glyoxylate. However, isotope-labelled carbon atoms from phenylethyl alcohol accumulated mainly in the pyridine ring of NAD(+)/NADH and NADP(-/)NADPH molecules, showing that these nucleotides were the main products of phenylethyl alcohol catabolism. Interestingly, two metabolic pathways where these nucleotides play an important role, nitrogen metabolism and nicotinate/nicotinamide metabolism, were also short-listed through our previous metabolomics works as metabolic pathways likely to be closely associated with C. albicans morphogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomass
  • Candida albicans / growth & development
  • Candida albicans / metabolism*
  • Carbon / metabolism
  • Culture Media / metabolism
  • Extracellular Space / metabolism
  • Hyphae / growth & development
  • Hyphae / metabolism*
  • Intracellular Space / metabolism
  • Metabolic Networks and Pathways
  • Metabolome
  • Metabolomics / methods
  • Phenylethyl Alcohol / metabolism*
  • Quorum Sensing

Substances

  • Culture Media
  • Carbon
  • Phenylethyl Alcohol

Grants and funding

This work was supported by University of Auckland Faculty of Science Research Funding and by the University of Auckland Doctoral Scholarship to Ting-Li Han. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.