ALS1 Deletion Increases the Proportion of Small Cells in a Candida albicans Culture Population: Hypothesizing a Novel Role for Als1
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY(2022)
Abstract
Candida albicans 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 ALS1 produced a strain that showed delayed germ-tube formation and delayed disease progression in a murine model of disseminated candidiasis. Populations of Delta als1/Delta als1 cultured cells had a higher proportion of smaller cells compared to wild-type or ALS1 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 Delta als1/Delta als1 cells with varied cell-size distributions. Delayed germ-tube formation was demonstrated for small cells sorted from a wild-type (ALS1/ALS1) culture population. Large cells sorted from a Delta als1/Delta als1 culture formed germ tubes as quickly as the wild-type control demonstrating clearly that the Delta als1/Delta als1 germ-tube formation delays were attributable to cell size. In vivo, 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 Delta als1/Delta als1 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 Delta als1/Delta als1 population increased cfu/g of tissue and showed increased lesion severity compared to the overall mutant cell population. In vivo hypha lengths from the large, sorted Delta als1/Delta als1 cells were comparable to those for the wild-type control strain. These results demonstrated that a large share of the Delta als1/Delta als1 in-vivo phenotype was attributable to cell size. Collectively, the data suggest a role for Als1 in C. albicans cell size homeostasis, a novel hypothesis for further exploration.
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Key words
Candida albicans,cell size,agglutinin-like sequence family,germ tube,murine model,disseminated candidiasis
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