Yeast and Filaments Have Specialized, Independent Activities in a Zebrafish Model of Candida albicans Infection

• Published in: Infection and immunity 2018-10, Vol.86 (10)
• Main Authors: Seman, Brittany G, Moore, Jessica L, Scherer, Allison K, Blair, Bailey A, Manandhar, Sony, Jones, Joshua M, Wheeler, Robert T
• Format: Article
• Language: English
• Subjects: Fungal and Parasitic Infections; Spotlight
• ISSN: 0019-9567; 1098-5522
• DOI: 10.1128/IAI.00415-18

dimorphism is a crucial virulence factor during invasive candidiasis infections, which claim the lives of nearly one-half of those afflicted. It has long been believed that filaments drive tissue invasion and yeast mediates bloodstream dissemination, but observation of these activities during infection has been prevented by technical limitations. We used a transparent zebrafish infection model to analyze more comprehensively how utilizes shape to disseminate and invade. This model facilitated the use of diverse, complementary strategies to manipulate shape, allowing us to monitor dissemination, invasion, and pathogenesis via intravital imaging of individual fungal cells throughout the host. To control fungal cell shape, we employed three different strategies: gene deletion ( Δ/Δ Δ/Δ, Δ/Δ), overexpression of master regulators ( or ), and modulation of the infection temperature (21°C, 28°C, or 33°C). The effects of these orthogonal manipulations were consistent, support the proposed specialized roles of yeast in dissemination and filaments in tissue invasion and pathogenesis, and indicate conserved mechanisms in zebrafish. To test if either morphotype changes the effectiveness of the other, we infected fish with a known mixture of shape-locked strains. Surprisingly, mixed-strain infections were associated with additive, but not synergistic, filament invasion and yeast dissemination. These findings provide the most complete view of morphotype-function relationships for to date, revealing independent roles of yeast and filaments during disseminated candidiasis.