ALS1 Deletion Increases the Proportion of Small Cells in a Candida albicans Culture Population: Hypothesizing a Novel Role for Als1

Als1 is a large cell-surface glycoprotein most often discussed for its role in mediating ligand-binding and aggregative interactions. Relative to a wild-type control, deletion of produced a strain that showed delayed germ-tube formation and delayed disease progression in a murine model of disseminated candidiasis. Populations of cultured cells had a higher proportion of smaller cells compared to wild-type or reintegrant control cultures. The goal of this work was to investigate whether this difference in cell-size distributions was responsible for delayed germ-tube formation and delayed disease progression. Flow cytometry was used to select populations of wild-type and cells with varied cell-size distributions. Delayed germ-tube formation was demonstrated for small cells sorted from a wild-type ( ) culture population. Large cells sorted from a culture formed germ tubes as quickly as the wild-type control demonstrating clearly that the germ-tube formation delays were attributable to cell size. , smaller-sized cells of the wild-type control showed fewer colony-forming units (cfu) per gram of kidney tissue and less-severe histopathology lesions compared to larger cells of the same strain. The strain showed reduced cfu/g of kidney tissue and less-severe lesions compared to the wild-type control. However, isolation and testing of the larger cells from the population increased cfu/g of tissue and showed increased lesion severity compared to the overall mutant cell population. hypha lengths from the large, sorted cells were comparable to those for the wild-type control strain. These results demonstrated that a large share of the phenotype was attributable to cell size. Collectively, the data suggest a role for Als1 in cell size homeostasis, a novel hypothesis for further exploration.