Deletion of the Candida albicans histidine kinase gene CHK1 improves recognition by phagocytes through an increased exposure of cell wall beta-1,3-glucans

Microbiology (Reading). 2010 Nov;156(Pt 11):3432-3444. doi: 10.1099/mic.0.040006-0. Epub 2010 Aug 5.


The pathogenic fungus Candida albicans is able to cover its most potent proinflammatory cell wall molecules, the β-glucans, underneath a dense mannan layer, so that the pathogen becomes partly invisible for immune cells such as phagocytes. As the C. albicans histidine kinases Chk1p, Cos1p and CaSln1p had been reported to be involved in virulence and cell wall biosynthesis, we investigated whether deletion of the respective genes influences the activity of phagocytes against C. albicans. We found that among all histidine kinase genes, CHK1 plays a prominent role in phagocyte activation. Uptake of the deletion mutant Δchk1 as well as the acidification of Δchk1-carrying phagosomes was significantly increased compared with the parental strain. These improved activities could be correlated with an enhanced accessibility of the mutant β-1,3-glucans for immunolabelling. In addition, any inhibition of β-1,3-glucan-mediated phagocytosis resulted in a reduced uptake of Δchk1, while ingestion of the parental strain was hardly affected. Moreover, deletion of CHK1 caused an enhanced release of interleukins 6 and 10, indicating a stronger activation of the β-1,3-glucan receptor dectin-1. In conclusion, the Chk1p protein is likely to be involved in masking β-1,3-glucans from immune recognition. As there are no homologues of fungal histidine kinases in mammals, Chk1p has to be considered as a promising target for new antifungal agents.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Candida albicans / enzymology
  • Candida albicans / genetics*
  • Candida albicans / immunology
  • Cell Line
  • Cell Wall / immunology*
  • Checkpoint Kinase 1
  • Fungal Proteins / genetics*
  • Gene Deletion
  • Humans
  • Interleukin-10 / immunology
  • Interleukin-6 / immunology
  • Lectins, C-Type
  • Mannans / immunology
  • Membrane Proteins / immunology
  • Mice
  • Nerve Tissue Proteins / immunology
  • Phagocytes / immunology*
  • Phagocytosis
  • Protein Kinases / genetics*
  • beta-Glucans / immunology*


  • Fungal Proteins
  • Interleukin-6
  • Lectins, C-Type
  • Mannans
  • Membrane Proteins
  • Nerve Tissue Proteins
  • beta-Glucans
  • dectin 1
  • Interleukin-10
  • beta-1,3-glucan
  • Protein Kinases
  • CHEK1 protein, human
  • Checkpoint Kinase 1
  • Chek1 protein, mouse