Developmental Expression of a Tandemly Repeated, Proline- and Glutamine-rich Amino Acid Motif on Hyphal Surfaces of Candida albicans

Abstract

cDNA sequences encoding a cell wall protein have been isolated from the opportunistic pathogen, Candida albicans, an organism that can cause serious disease in immunocompromised patients such as those with AIDS. The cDNA encodes a peptide that is largely composed of an acidic, repeated motif 10 amino acids in length that is rich in proline and glutamine residues. The cDNA gene product was found to be present on hyphal surfaces by immunofluorescence assays using monospecific antisera raised to the recombinant protein produced in Pichia pastoris. The hyphae-specific surface location was also seen on organisms colonizing the gastrointestinal mucosa of mice, indicating that the antigen is produced and developmentally regulated during growth in host tissues. The cDNA clone hybridized to an abundant messenger RNA 2.3 kilobases in size that was present in hyphal but not yeast forms. These studies demonstrate that the bud-hypha transition is accompanied by the de novo synthesis of proteins that are targeted to hyphal surfaces. The primary sequence of the unique amino acid motif shares features with surface proteins of other lower eukaryotic microorganisms and with host acidic salivary proline-rich proteins.

Expression cloning of a fungal proline‐rich glycoprotein specific to the biotrophic interface formed in the Colletotrichum–bean interaction

“…Proline-rich proteins are important structural components of plant cell walls, but few such proteins have been identified in fungi. Recently, a gene encoding a putative proline-rich protein was isolated from another biotrophic fungus, E. graminis (Justesen et al, 1996) and proline-rich proteins have been identified in C. graminicola and Candida albicans (Nicholson et al, 1986;Staab et al, 1996). The proline-rich proteins (PRPs) and hydroxyproline-rich glycoproteins (HRGPs), found in plant cell walls characteristically have repetitive motifs, although these differ from those found in the CIH1 polypeptide.…”

Identification of inhibitors of yeast-to-hyphae transition in Candida albicans by a reporter screening assay

“…It codes for the adhesin Hwp1p, which was detected in the cell wall of hyphae but never of blastoconidia. Likewise, the HWP1-transcript is only present after commitment to hyphal growth (Staab et al, 1996(Staab et al, , 1999.…”

Candida albicans HWP1 gene expression and host antibody responses in colonization and disease

“…Hyphal wall protein (Hwp1), a transglutaminase substrate which functions as an adhesin, is important for the pathogenesis of candidiasis (Staab et al, 1996(Staab et al, , 1999Sundstrom et al, 2002). HWP1 mRNA and protein are abundant in hyphae in vitro, and greatly reduced or undetectable in yeast forms (Staab et al, 1996(Staab et al, , 1999 Sharkey et al, 1999;Nantel et al, 2002).…”

“…HWP1 mRNA and protein are abundant in hyphae in vitro, and greatly reduced or undetectable in yeast forms (Staab et al, 1996(Staab et al, , 1999 Sharkey et al, 1999;Nantel et al, 2002). Hypha-specific expression of Hwp1 extends to fungal growth in the host, as shown by the presence and absence of Hwp1 on hyphae and yeast, respectively, in candidiasis of the murine stomach (Sundstrom et al, 2002).…”

“…colonization, among inhibitory microbial flora, to frequent occurrence of asymptomatic oral and vaginal carriage, and to virulence in immunocompetent and immunodeficient hosts, are poorly understood. In previous work, we have found that expression of specific secreted aspartyl proteinase (SAP) genes is correlated with active disease and anatomical location, whereas expression of other SAP genes reflects the presence of the organism but not disease (Naglik et al, 2003).Hyphal wall protein (Hwp1), a transglutaminase substrate which functions as an adhesin, is important for the pathogenesis of candidiasis (Staab et al, 1996(Staab et al, , 1999Sundstrom et al, 2002). HWP1 mRNA and protein are abundant in hyphae in vitro, and greatly reduced or undetectable in yeast forms (Staab et al, 1996(Staab et al, , 1999 Sharkey et al, 1999;Nantel et al, 2002).…”