Moonlighting proteins as virulence factors of pathogenic fungi, parasitic protozoa and multicellular parasites

Mol Oral Microbiol. 2014 Dec;29(6):270-83. doi: 10.1111/omi.12078. Epub 2014 Sep 19.


The delicate balance between eukaryotic pathogens and their human hosts during the initiation and development of infection is a complex process involving many diverse interactions. Different infectious agents, including pathogenic fungi, parasitic protozoa and multicellular parasites, directly interact through their cell surface with epithelial or endothelial cells of the human host as well as various proteinaceous host ligands such as extracellular matrix or plasma proteins. Eukaryotic pathogens possess a number of virulence factors but a relatively recently recognized and particularly interesting group of factors capable of enhancing virulence is the set of so-called 'moonlighting proteins'. This term was coined for a relatively large collection of housekeeping enzymes lacking special targeting motifs that would determine their extracellular localization, but that are often present at the cell surface of pathogen. Several such enzymes with key metabolic functions in glycolysis, the pentose phosphate cycle or other fundamental intracellular processes perform entirely new, non-catalytic roles often associated with adhesion to host ligands. Our current study summarizes some of the current knowledge of interesting moonlighting proteins which play putative or confirmed roles as virulence factors in pathogenic fungi, parasitic protozoa and multicellular parasites.

Keywords: Candida; Paracoccidioides; Plasmodium; Schistosoma; housekeeping enzymes; protein moonlighting.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Blood Proteins / biosynthesis*
  • Blood Proteins / metabolism
  • Cell Adhesion
  • Enzymes / biosynthesis
  • Enzymes / metabolism*
  • Extracellular Matrix / metabolism
  • Fungal Proteins / metabolism*
  • Fungi / enzymology
  • Fungi / pathogenicity*
  • Glycolysis / physiology
  • Homeostasis / physiology
  • Humans
  • Ligands
  • Molecular Chaperones / biosynthesis
  • Molecular Chaperones / physiology
  • Parasites / enzymology
  • Parasites / pathogenicity*
  • Protozoan Proteins / metabolism*
  • Ribosomal Proteins / physiology
  • Virulence
  • Virulence Factors / biosynthesis
  • Virulence Factors / metabolism*


  • Blood Proteins
  • Enzymes
  • Fungal Proteins
  • Ligands
  • Molecular Chaperones
  • Protozoan Proteins
  • Ribosomal Proteins
  • Virulence Factors