Molecular analysis of CaMnt1p, a mannosyl transferase important for adhesion and virulence of Candida albicans.
There is an immediate need for identification of new antifungal targets in opportunistic pathogenic fungi like Candida albicans. In the past, efforts have focused on synthesis of chitin and glucan, which confer mechanical strength and rigidity upon the cell wall. This paper describes the molecular analysis of CaMNT1, a gene involved in synthesis of mannoproteins, the third major class of macromolecule found in the cell wall. CaMNT1 encodes an alpha-1, 2-mannosyl transferase, which adds the second mannose residue in a tri-mannose oligosaccharide structure which represents O-linked mannan in C. albicans. The deduced amino acid sequence suggests that CaMnt1p is a type II membrane protein residing in a medial Golgi compartment. The absence of CaMnt1p reduced the ability of C. albicans cells to adhere to each other, to human buccal epithelial cells, and to rat vaginal epithelial cells. Both heterozygous and homozygous Camnt1 null mutants of C. albicans showed strong attenuation of virulence in guinea pig and mouse models of systemic candidosis, which, in guinea pigs, could be attributed to a decreased ability to reach and/or adhere internal organs. Therefore, correct CaMnt1p-mediated O-linked mannosylation of proteins is critical for adhesion and virulence of C. albicans.
Buurman
E T
ET
Department of Molecular and Cell Biology, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, United Kingdom.
Westwater
C
C
Hube
B
B
Brown
A J
AJ
Odds
F C
FC
Gow
N A
NA
D000595:Amino Acid Sequence; D000818:Animals; D002176:Candida albicans / Q000201:enzymology / Q000472:pathogenicity*; D002181:Candidiasis, Vulvovaginal / Q000382:microbiology; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D002448:Cell Adhesion; D004847:Epithelial Cells / Q000382:microbiology; D005260:Female; D006031:Glycosylation; D006168:Guinea Pigs; D006801:Humans; D008364:Mannosyltransferases / Q000235:genetics* / Q000502:physiology; D051379:Mice; D008969:Molecular Sequence Data; D051381:Rats; D029701:Saccharomyces cerevisiae Proteins
D029701:Saccharomyces cerevisiae Proteins; C068701:KRE2 protein, S cerevisiae; D008364:Mannosyltransferases