Autophagy in the pathogen Candida albicans.
Autophagy is a major cellular process that facilitates the bulk degradation of eukaryotic macromolecules and organelles, through degradation within the lysosomal/vacuole compartment. This has been demonstrated to influence a diverse array of eukaryotic cell functions including adaptation, differentiation and developmental programmes. For example, in Saccharomyces cerevisiae autophagy is required for sporulation and survival of nitrogen starvation. The opportunistic pathogen Candida albicans has the ability to colonize and cause disease within a diverse range of mammalian host sites. The ability to adapt and differentiate within the host is liable to be critical for host colonization and infection. Previous results indicated that the vacuole plays an important role in C. albicans adaptation to stress, differentiation, and survival within and injury of host cells. In this study the importance of vacuole-mediated degradation through the process of autophagy was investigated. This involved identification and deletion of ATG9, a C. albicans gene required for autophagy. The deletion strain was blocked in autophagy and the closely related cytoplasm to vacuole (cvt) trafficking pathway. This resulted in sensitivity to nitrogen starvation, but no defects in growth rate, vacuole morphology or resistance to other stresses. This indicates that the mutant has specific defects in autophagy/cvt trafficking. Given the importance of autophagy in the development and differentiation of other eukaryotes, it was surprising to find that the atg9Delta mutant was unaffected in either yeast-hypha or chlamydospore differentiation. Furthermore, the atg9Delta mutant survived within and killed a mouse macrophage-like cell line as efficiently as control strains. The data suggest that autophagy plays little or no role in C. albicans differentiation or during interaction with host cells.
Palmer
Glen E
GE
Department of MIP, Louisiana State University Health Sciences Center School of Dentistry, 1100 Florida Avenue, Box F8-130, New Orleans, LA 70119, USA. gpalme@lsuhsc.edu
Kelly
Michelle N
MN
Sturtevant
Joy E
JE
D000222:Adaptation, Physiological; D000818:Animals; D001343:Autophagy; D002176:Candida albicans / Q000502:physiology*; D002177:Candidiasis / Q000382:microbiology; D002460:Cell Line; D005656:Fungal Proteins / Q000502:physiology; D008264:Macrophages / Q000382:microbiology; D008565:Membrane Proteins / Q000502:physiology; D051379:Mice; D014617:Vacuoles / Q000382:microbiology
D005656:Fungal Proteins; D008565:Membrane Proteins