Source Publication
PLOS Genetics
Document Type
Article
Publication Date
1-31-2019
DOI
0.1371/journal.pgen.1007892
Abstract
Candida albicans is among the most common causes of human fungal infections and is an important source of mortality. C. albicans is able to diminish its detection by innate immune cells through masking of β (1,3)-glucan in the inner cell wall with an outer layer of heavily glycosylated mannoproteins (mannan). However, mutations or drugs that disrupt the cell wall can lead to exposure of β (1,3)-glucan (unmasking) and enhanced detection by innate immune cells through receptors like Dectin-1, the C-type signaling lectin. Previously, our lab showed that the pathway for synthesizing the phospholipid phosphatidylserine (PS) plays a role in β (1,3)-glucan masking. The homozygous PS synthase knockout mutant, cho1Δ/Δ, exhibits increased exposure of β (1,3)-glucan. Several Mitogen Activated Protein Kinase (MAPK) pathways and their upstream Rho-type small GTPases are important for regulating cell wall biogenesis and remodeling. In the cho1Δ/Δ mutant, both the Cek1 and Mkc1 MAPKs are constitutively activated, and they act downstream of the small GTPases Cdc42 and Rho1, respectively. In addition, Cdc42 activity is up-regulated in cho1Δ/Δ. Thus, it was hypothesized that activation of Cdc42 or Rho1 and their downstream kinases cause unmasking. Disruption of MKC1 does not decrease unmasking in cho1Δ/Δ, and hyperactivation of Rho1 in wild-type cells increases unmasking and activation of both Cek1 and Mkc1. Moreover, independent hyperactivation of the MAP kinase kinase kinase Ste11 in wild-type cells leads to Cek1 activation and increased β (1,3)-glucan exposure. Thus, upregulation of the Cek1 MAPK pathway causes unmasking, and may be responsible for unmasking in cho1Δ/Δ.
Recommended Citation
Chen T, Jackson JW, Tams RN, Davis SE, Sparer TE, Reynolds TB (2019) Exposure of Candida albicans β (1,3)-glucan is promoted by activation of the Cek1 pathway. PLoS Genetics 15(1): e1007892. https://doi.org/10.1371/journal. pgen.1007892
Submission Type
Publisher's Version
S2 Table. Plasmids used in this study pgen.1007892.s002.docx (15 kB)
S3 Table. Primers used in this study pgen.1007892.s003.xlsx (12 kB)
S1 Text. Plasmid and Strain Construction pgen.1007892.s004.docx (22 kB)
S1 Fig. The STE11ΔN467 strain exhibits significantly increased β (1,3)-glucan exposure compared to wild-type pgen.1007892.s005.tif (273 kB)
S2 Fig. Growth curves were measured to determine the growth rate of strains in YPD vs YPM pgen.1007892.s006.tif (247 kB)
S3 Fig. The exposed β (1,3)-glucan in STE11ΔN467 YPM cells was not restricted to bud scars pgen.1007892.s007.tif (1800 kB)
S4 Fig. CDC42G12V increases β (1,3)-glucan exposure, but also reduces the viable cell population pgen.1007892.s008.tif (830 kB)
S5 Fig. MKC1 was knocked out in C. albicans via CRISPR-Cas9 pgen.1007892.s009.tif (194 kB)
S6 Fig. Deleting one PKC1 allele in cho1Δ:Δ did not rescue β (1,3)-glucan exposure pgen.1007892.s010.tif (249 kB)
Comments
This article was published openly thanks to the University of Tennessee Open Publishing Support Fund.
Licensed under a Creative Commons Attribution 4.0 International license.