Active substances: Doxycycline
The regulation of the epigenetic white-opaque switch has been examined in detail and involves distinct transcriptional networks in the two cell types.
Z Hnisz et al. Despite a detailed understanding of the mechanism of white-opaque switching, there is limited information about how white and opaque cell types differ in their interactions with the host. In vitro studies suggest that opaque cells are more susceptible to killing by neutrophils than white cells, and also stimulate greater superoxide production Kolotila and Diamond, 1990, whereas only white cells release a chemoattractant for neutrophils Geiger et al.
Furthermore, white cells are more efficiently phagocytosed by macrophages and neutrophils than opaque cells in vitro Lohse and Johnson,; Sasse et al. In contrast, both cell types are phagocytosed with equal efficiency by dendritic cells Sasse et al.
In addition to differential interactions with immune cells, white and opaque cell types exhibit different niche specificities during infection of a mammalian host. Opaque cells preferentially colonize the skin Lachke et al.Here, we address the in vivo albicans, cells exhibit heritable switching between states in a zebrafish model of which yield differences in mating, filamentous in vitro.
Despite these studies, questions remain as to the precise roles of white and opaque cells during infection, as well as the traits of the two cell types that give rise to different properties in vivo.
Zebrafish Danio rerio have been developed as an alternative model system for understanding interactions between microbial pathogens and the vertebrate host Torraca et al.
Experimental models using egg, larval, and adult zebrafish have been developed for C. Additionally, the innate immune system of the zebrafish, which is comprised of macrophages, neutrophils, complement, and Toll-like receptors TLRs Seeger et al.
Adaptive immunity develops approximately 2—3 weeks post-fertilization Willett et al.
The transparency of zebrafish also permits direct, non-invasive visualization of both host and microbial cells at early life stages Meeker and Trede,; Knox et al. Previous experiments infected zebrafish with C. In this study, we compare and contrast the ability of white and opaque forms of C.
These experiments compare infection, filamentation, dissemination, phagocytosis, and virulence by both cellular states, and contrast these properties over a range of host temperatures.
Both white and opaque cells formed filaments in vivo, which is the first demonstration that opaque cells can undergo filamentation inside a vertebrate host. Analysis of mutants unable to undergo filamentation show that this program contributes to virulence by both white and opaque cells.
We discuss these differences in light of the role of pathogen-phagocyte interactions in promoting susceptibility to lethal infection by C. Materials and Methods C.
Media was prepared as described Guthrie.
Strain list. Transformants were selected by growth on nourseothricin and verified by PCR.