Loss of cell wall mannosylphosphate in Candida albicans does not influence macrophage recognition.
The outer layer of the cell wall of the human pathogenic fungus Candida albicans is enriched with heavily mannosylated glycoproteins that are the immediate point of contact between the fungus and cells of the host, including phagocytes. Previous work had identified components of the acid-labile fraction of N-linked mannan, comprising beta-1,2-linked mannose residues attached via a phosphodiester bond, as potential ligands for macrophage receptors and modulators of macrophage function. We therefore isolated and disrupted the CaMNN4 gene, which is required for mannosyl phosphate transfer and hence the attachment of beta-1,2 mannose oligosaccharides to the acid-labile N-mannan side chains. With the mannosylphosphate eliminated, the mnn4Delta null mutant was unable to bind the charged cationic dye Alcian Blue and was devoid of acid-labile beta-1,2-linked oligomannosaccharides. The mnn4Delta mutant was unaffected in cell growth and morphogenesis in vitro and in virulence in a murine model of systemic C. albicans infection. The null mutant was also not affected in its interaction with macrophages. Mannosylphosphate is therefore not required for macrophage interactions or for virulence of C. albicans.
Hobson
Richard P
RP
School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Aberdeen, AB25 2ZD, United Kingdom.
Munro
Carol A
CA
Bates
Steven
S
MacCallum
Donna M
DM
Cutler
Jim E
JE
Heinsbroek
Sigrid E M
SE
Brown
Gordon D
GD
Odds
Frank C
FC
Gow
Neil A R
NA
D000423:Alcian Blue; D000818:Animals; D002176:Candida albicans / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D002177:Candidiasis / Q000276:immunology* / Q000382:microbiology; D002460:Cell Line; D002473:Cell Wall / Q000378:metabolism; D004396:Coloring Agents; D005260:Female; D008264:Macrophages / Q000166:cytology / Q000276:immunology* / Q000382:microbiology*; D008297:Male; D008360:Mannosephosphates / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D016296:Mutagenesis; D009154:Mutation; D009844:Oligosaccharides / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000276:immunology; D014774:Virulence
D004396:Coloring Agents; C105147:MNN4 protein, S cerevisiae; D008360:Mannosephosphates; D008565:Membrane Proteins; D009844:Oligosaccharides; D029701:Saccharomyces cerevisiae Proteins; C028569:oligomannoside; D000423:Alcian Blue