Endoplasmic reticulum alpha-glycosidases of Candida albicans are required for N glycosylation, cell wall integrity, and normal host-fungus interaction.
The cell surface of Candida albicans is enriched in highly glycosylated mannoproteins that are involved in the interaction with the host tissues. N glycosylation is a posttranslational modification that is initiated in the endoplasmic reticulum (ER), where the Glc(3)Man(9)GlcNAc(2) N-glycan is processed by alpha-glucosidases I and II and alpha1,2-mannosidase to generate Man(8)GlcNAc(2). This N-oligosaccharide is then elaborated in the Golgi to form N-glycans with highly branched outer chains rich in mannose. In Saccharomyces cerevisiae, CWH41, ROT2, and MNS1 encode for alpha-glucosidase I, alpha-glucosidase II catalytic subunit, and alpha1,2-mannosidase, respectively. We disrupted the C. albicans CWH41, ROT2, and MNS1 homologs to determine the importance of N-oligosaccharide processing on the N-glycan outer-chain elongation and the host-fungus interaction. Yeast cells of Cacwh41Delta, Carot2Delta, and Camns1Delta null mutants tended to aggregate, displayed reduced growth rates, had a lower content of cell wall phosphomannan and other changes in cell wall composition, underglycosylated beta-N-acetylhexosaminidase, and had a constitutively activated PKC-Mkc1 cell wall integrity pathway. They were also attenuated in virulence in a murine model of systemic infection and stimulated an altered pro- and anti-inflammatory cytokine profile from human monocytes. Therefore, N-oligosaccharide processing by ER glycosidases is required for cell wall integrity and for host-fungus interactions.
Mora-Montes
Héctor M
HM
Instituto de Investigación en Biología Experimental, Facultad de Química, Universidad de Guanajuato, Apartado Postal 187, Guanajuato, Gto. CP 36000, México.
Bates
Steven
S
Netea
Mihai G
MG
Díaz-Jiménez
Diana F
DF
López-Romero
Everardo
E
Zinker
Samuel
S
Ponce-Noyola
Patricia
P
Kullberg
Bart Jan
BJ
Brown
Alistair J P
AJ
Odds
Frank C
FC
Flores-Carreón
Arturo
A
Gow
Neil A R
NA
D000818:Animals; D002176:Candida albicans / Q000201:enzymology*; D002473:Cell Wall / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000201:enzymology*; D005260:Female; D006026:Glycoside Hydrolases / Q000378:metabolism / Q000502:physiology*; D006031:Glycosylation; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008954:Models, Biological; D009000:Monocytes / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000201:enzymology*; D014774:Virulence
D016207:Cytokines; D006026:Glycoside Hydrolases