Cross-feeding and interkingdom communication in dual-species biofilms of Streptococcus mutans and Candida albicans

ISME J. 2014 Nov;8(11):2256-71. doi: 10.1038/ismej.2014.73. Epub 2014 May 13.


Polymicrobial biofilms are of large medical importance, but relatively little is known about the role of interspecies interactions for their physiology and virulence. Here, we studied two human pathogens co-occuring in the oral cavity, the opportunistic fungus Candida albicans and the caries-promoting bacterium Streptococcus mutans. Dual-species biofilms reached higher biomass and cell numbers than mono-species biofilms, and the production of extracellular polymeric substances (EPSs) by S. mutans was strongly suppressed, which was confirmed by scanning electron microscopy, gas chromatography-mass spectrometry and transcriptome analysis. To detect interkingdom communication, C. albicans was co-cultivated with a strain of S. mutans carrying a transcriptional fusion between a green fluorescent protein-encoding gene and the promoter for sigX, the alternative sigma factor of S. mutans, which is induced by quorum sensing signals. Strong induction of sigX was observed in dual-species biofilms, but not in single-species biofilms. Conditioned media from mixed biofilms but not from C. albicans or S. mutans cultivated alone activated sigX in the reporter strain. Deletion of comS encoding the synthesis of the sigX-inducing peptide precursor abolished this activity, whereas deletion of comC encoding the competence-stimulating peptide precursor had no effect. Transcriptome analysis of S. mutans confirmed induction of comS, sigX, bacteriocins and the downstream late competence genes, including fratricins, in dual-species biofilms. We show here for the first time the stimulation of the complete quorum sensing system of S. mutans by a species from another kingdom, namely the fungus C. albicans, resulting in fundamentally changed virulence properties of the caries pathogen.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / genetics
  • Bacteriocins / genetics
  • Biofilms*
  • Candida albicans / genetics
  • Candida albicans / growth & development
  • Candida albicans / physiology*
  • Candida albicans / ultrastructure
  • Polysaccharides, Bacterial / biosynthesis
  • Quorum Sensing / genetics
  • Sigma Factor / genetics
  • Streptococcus mutans / genetics
  • Streptococcus mutans / growth & development
  • Streptococcus mutans / physiology*
  • Streptococcus mutans / ultrastructure


  • Bacterial Proteins
  • Bacteriocins
  • Polysaccharides, Bacterial
  • Sigma Factor