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 target s 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 nail. This paper descr ibes the molecular analysis of CaMNT1, a gene involved in synthesis of mannoproteins, the third major class of macromolecule found in the ce ll 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 aci d sequence suggests that CaMnt1p is a type II membrane protein residin g in a medial Golgi compartment, The absence of CaMnt1p reduced the ab ility of C. albicans cells to adhere to each other, to human buccal ep ithelial cells, and to rat vaginal epithelial cells. Both heterozygous and homozygous Camnt1 null mutants of C. albicans showed strong atten uation of virulence in guinea pig and mouse models of systemic candido sis, which, in guinea pigs, could be attributed to a decreased ability to reach and/or adhere internal organs, Therefore, correct CaMnt1p-me diated O-linked mannosylation of proteins is critical for adhesion and virulence of C. albicans.