Fungal cell wall surface protein (CWP)

Fungal cell wall surface proteins and lectins are a diverse group of glycoproteins, primarily mannoproteins, that constitute the outermost layer of the fungal cell wall. These proteins, many of which are anchored to the cell wall via glycosylphosphatidylinositol (GPI) remnants, are essential for fungal pathogenesis, mediating adhesion to host tissues and medical devices, and facilitating the formation of biofilms. Lectin-like proteins, such as the Agglutinin-Like Sequence (Als) family in Candida albicans, play a pivotal role in colonization and invasion by recognizing and binding to host cell surface carbohydrates. Because these surface components are unique to fungi and critical for virulence, they are targeted by emerging therapeutic strategies, including vaccines like NDV-3A and monoclonal antibodies that aim to neutralize adhesins or promote opsonization. Additionally, small molecules like manogepix indirectly target these proteins by inhibiting the Gwt1 enzyme required for their GPI-anchoring, thereby preventing their localization to the cell surface and weakening the fungal defense against the host immune system.

Other names

Fungal adhesinMannoproteinCell wall proteinLectin-like proteinGPI-anchored proteinFibrillar protein coatAgglutinin-like sequence protein

Inhibition of GPI-anchor synthesis, inhibition of protein glycosylation, opsonization, and inhibition of adhesion.