Analysis of autophagy during infections of Cryptococcus neoformans.

Cryptococcus neoformans is a yeastlike fungus that causes a lethal meningoencephalitis in a broad spectrum of immunocompromised patients and has become the most common cause of meningitis due to AIDS-related infections in Africa. Key to the development of new agents to control and prevent this infection is the identification of cellular mechanisms required for pathogenesis. Survival of the fungus within the hostile and nutrient-deprived environments of the host has recently been shown to depend on the induction of autophagy, whereby the cell recycles nutrients by slowly digesting itself in a regulated fashion.

Adequate phenylalanine synthesis mediated by G protein is critical for protection from UV radiation damage in young etiolated Arabidopsis thaliana seedlings.

Etiolated Arabidopsis thaliana seedlings, lacking a functional prephenate dehydratase1 gene (PD1), also lack the ability to synthesize phenylalanine (Phe) and, as a consequence, phenylpropanoid pigments. We find that low doses of ultraviolet (UV)-C (254 nm) are lethal and low doses of UV-B cause severe damage to etiolated pd1 mutants, but not to wild-type (wt) seedlings. Furthermore, exposure to UV-C is lethal to etiolated gcr1 (encoding a putative G protein-coupled receptor in Arabidopsis) mutants and gpa1 (encoding the sole G protein alpha subunit in Arabidopsis) mutants.

PI3K signaling of autophagy is required for starvation tolerance and virulenceof Cryptococcus neoformans.

Autophagy is a process by which cells recycle cytoplasm and defective organelles during stress situations such as nutrient starvation. It can also be used by host cells as an immune defense mechanism to eliminate infectious pathogens. Here we describe the use of autophagy as a survival mechanism and virulence-associated trait by the human fungal pathogen Cryptococcus neoformans.

C. elegans peb-1 mutants exhibit pleiotropic defects in molting, feeding, and morphology.

Caenorhabditis elegans PEB-1 is a novel DNA-binding protein expressed in most pharyngeal cell types and outside the pharynx in the hypodermis, hindgut, and vulva. Previous RNAi analyses indicated that PEB-1 is required for normal morphology of these tissues and growth; however, the peb-1 null phenotype was unknown. Here we describe the deletion mutant peb-1(cu9) that not only exhibits the morphological defects observed in peb-1(RNAi) animals, but also results in penetrant larval lethality characterized by defects in pharyngeal function and molting.

Copper-mediated reversal of defective laccase in a Deltavph1 avirulent mutant of Cryptococcus neoformans.

Previous studies have shown that a Deltavph1 Cryptococcus neoformans mutant defective in vesicular acidification lacked several important virulence factors including a copper-containing laccase and was avirulent in a mouse model. In the present studies, we characterized laccase transcription and protein production to obtain insights into the mechanism of the vph1 mutation in this pathogen. Although transcription and protein expression were somewhat reduced, laccase protein was found to be successfully translated and correctly targeted to the cell wall in the Deltavph1 mutant as shown by Western blot and immuno-electron microscopy, despite a complete lack of laccase activity.