Dynamics of Agglutinin -Like Sequence (Als) Protein Localization on the Surface of Candida Albicans

146 p.Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 2009.The ALS gene family encodes large cell-surface glycoproteins associated with C. albicans pathogenesis. Als proteins are thought to act as adhesin molecules binding to host tissues. Wide variation in expression levels among the ALS genes exists and is related to cell morphology and environmental conditions. ALS1, ALS3, and ALS4 are three of the four most highly expressed ALS genes. This work describes the production and use of specific high affinity monoclonal antibodies against Als1, Als3, and Als4 to evaluate protein production and localization at both the individual cell and population levels. Production and localization of these proteins is tightly regulated and occurs under specific growth conditions. When examined at a population level, it is clear that cells from the same culture can have different profiles of Als proteins on the cell surface. These results provide a very different view of the Als family than the view held by those who suggest that the Als family functions in antigenic variation in a classical sense. The monoclonal antibodies were also used to screen a diverse group of C. albicans strains and other Candida species for the presence of Als proteins or Als-like epitopes. Additionally, Als3 binding to several host proteins proposed to act as ligands for Als3 during C. albicans infection was characterized. Estimation of the number of Als1, Als3, and Als4 molecules on the cell surface allows evaluation of the potential role of Als3 binding to proposed host tissue ligands in C. albicans pathogenesis.U of I OnlyRestricted to the U of I community idenfinitely during batch ingest of legacy ETD