Summary Our published research has focused upon the role of Goa1p, an apparent regulator of the Candida albicans mitochondrial complex I (CI). Lack of Goa1p effects optimum cell growth, CI activity, and virulence. Eukaryotic CI is composed of a core of 14 alpha-proteobacterial subunit proteins and a variable number of supernumerary subunit proteins. Of the latter group of proteins, one (NUZM) is fungal-specific, and a second (NUXM) is found in fungi, algae and plants but is not a mammalian CI subunit protein. We have established that NUXM is orf19.6607 and NUZM is orf19.287 in C. albicans. Herein, we validate both subunit proteins as NADH:ubiquinone oxidoreductases (NUO) and annotate their gene functions. To accomplish these objectives, we compared null mutants of each with WT and gene-reconstituted strains. Genetic mutants of genes NUO1 (19.6607) and NUO2 (19.287), not surprisingly, each had reduced oxygen consumption, decreased mitochondrial redox potential, decreased CI activity, increased reactive oxidant species (ROS), and a decrease in chronological aging in vitro. Loss of either gene results in a disassembly of CI. Transcriptional profiling of both mutants indicated significant down regulation of genes of carbon metabolism, as well as upregulation of mitochondrial-associated gene families which may occur to compensate for the loss of CI activity. Profiling of both mutants also demonstrated a loss of cell wall β-mannosylation but not in a conserved CI subunit (ndh51Δ). The profiling data may indicate specific functions driven by the enzymatic activity of Nuo1p and Nuo2p. Of importance, each mutant is also avirulent in a murine blood-borne, invasive model of candidiasis associated with their reduced colonization of tissues. Based upon their fungal-specificity and roles in virulence, we suggest both as drug targets for antifungal drug discovery.

An effective method for grafting L-lactide (LA) from unmodified cellulose by ring-opening polymerization (ROP) in homogeneous mild conditions is presented. By using 4-dimethylaminopyridine (DMAP) as an organic catalyst, cellulose-graft-poly(L-lactide) (cellulose-g-PLLA) copolymers with a molar substitution (MS(PLLA)) of PLLA in a range of 0.99-12.28 were successfully synthesized in ionic liquid 1-allyl-3-methylimidazolium chloride (AmimCl) at 80 degrees C. The amount and length of grafted PLLA in cellulose-g-PLLA copolymers were controlled by adjusting the molar ratios of LA monomer to cellulose. The structure and thermal properties of cellulose-g-PLLA copolymers were characterized by (1)H NMR, (13)C NMR, wide-angle X-ray powder diffraction (WAXD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and optical microscopy. The DSC results revealed that the copolymers exhibited a single glass transition temperature, T(g), which sharply decreased with the increase of MS(PLLA) up to MS(PLLA) = 8.28 (DS(PLLA) = 2.19) and increased a little with a further increase of the lactyl content. When MS(PLLA) was above 4.40, the graft copolymers exhibited thermoplastic behavior, indicating the intermolecular and intramolecular hydrogen bonds in cellulose molecules had been effectively destroyed. By using a conventional thermal processing method, fibers and disks of cellulose-g-PLLA copolymers were prepared.