Alistair Jp Brown

..Candida albicans also adapts to hyperosmolarity via a HOG signaling network. However, it remains unknown whether Hog1 exerts integral or proportional control over glycerol production in C. albicans...

..Indeed, we observed a poor correlation between the transcriptome and phenome for those genes that were regulated during kidney infection and that have been virulence tested...

..Using this HSF1 CE2 deletion mutant we demonstrate that Hsf1 activation, and hence thermal adaptation, contributes significantly to the virulence of C. albicans...

..During amino acid starvation, levels of ternary complex are reduced. This overcomes the GCN4 translation attenuation effect via a scanning/reinitiation control mechanism dependent upon uORF spacing...

..However, there is, as yet, no formally accepted standard representation to support the sharing of proteomics data, and little systematic dissemination of comprehensive proteomic data sets...

..These fungi, which include ascomycetes, basidiomycetes and microsporidia, occupy highly divergent niches from saline environments to plant or mammalian hosts...

..These studies, together with analyses of C. albicans mutants, indicate that physiological fitness plays a central role in the pathogenicity of this fungus, alongside virulence factors...

..The regulatory networks that control morphogenesis are being elucidated; however, the primary signals that trigger morphogenesis remain obscure, and the physiological outputs of these networks are complex...

..A report of the symposium on Signaling and Systems Biology held during the Society for General Microbiology Spring Meeting, 29-30 March 2010, Edinburgh, UK...

..Hsf1 also regulates the expression of Hsp90, which controls the yeast-hypha transition in C. albicans, and we argue, might also control morphogenesis in other fungal pathogens of humans...

..In contrast, there is a high degree of commonality in the cellular responses to reactive oxygen and nitrogen species evoked in evolutionarily divergent fungal pathogens...

..The data suggest that, upon entering the bloodstream, C. albicans cells respond to glucose increasing their resistance to the oxidative and cationic stresses central to the armory of immunoprotective phagocytic cells...

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..albicans. One isolate of the fungus showed an opposite response...

..albicans has diverged from corresponding networks in model yeasts and that the C. albicans SAPK pathway functions in parallel with other pathways to regulate the core transcriptional response to stress...

..We have also shown that the Hog1 stress-activated mitogen-activated protein kinase, which is activated in response to the stresses examined in this study, makes a major contribution to the C. albicans stress proteome...

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..In a murine model of systemic infection, the null mutant was severely attenuated in virulence. These results demonstrate the importance of glycosylation for cell wall structure and virulence of C. albicans...

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..albicans genomic sequences that increase salt tolerance in C. dubliniensis. Introduction of a single copy of CaENA21 was subsequently shown to be sufficient to confer salt tolerance upon C. dubliniensis...

..albicans was independent of the recognition of beta-glucans by dectin-1. In conclusion, C. albicans induces production of monocyte-derived and T cell-derived cytokines through distinct pathways dependent on or independent of dectin-1...

..Data quality issues are considered throughout the lifecycle of a proteomics experiment, from experiment design and technique selection, through data analysis, to archiving and sharing...

..This review describes the targets and mechanisms of action of all classes of antifungal agents in clinical use or with clinical potential...

..We conclude that an antifungal drug directed against Fba1p would have to be potent to be effective...

..This review considers the role of morphogenesis in fungal infection and argues that no simple, universal relationship can be drawn between morphology and the invasive potential of a fungus...

..The study has extended the range of properties known to differ between C. albicans clades and suggests a possible but minor role of phosphate metabolism in the virulence of the species...

..This is the first report demonstrating an essential role for chitin synthase phosphorylation in the polarised biosynthesis of fungal cell walls and suggests a new mechanism for the regulation of this class of glycosyl-transferase enzyme...

..Comparative genomic analysis highlights genes that may contribute to C. albicans survival and its fitness as a human commensal and pathogen...

..Therefore, at least three pathways co-ordinately regulate chitin synthesis and activation of chitin synthesis operates at both transcriptional and post-transcriptional levels...

..We conclude that complex, multifactorial local responses offset and obscure any differences resulting from differences in surface mannosylation of C. albicans strains when infection results from pathology-standardized challenges...

..The double mutant was attenuated in virulence, underlining the importance of O-glycosylation in pathogenesis of C. albicans infections...

..albicans cells but not with live cells. Therefore, chitin is normally not exposed to cells of the innate immune system but is capable of influencing immune recognition by blocking dectin-1-mediated engagement with fungal cell walls...

..To test this hypothesis, we determined the effects of subinhibitory concentrations of three antifungal agents on expression of three secreted proteinase genes associated with virulence in filamentous forms of Candida albicans...

..Therefore, the MNT1/KRE2 gene family participates in three types of protein mannosylation in C. albicans, and these modifications play vital roles in fungal cell wall structure and cell surface recognition by the innate immune system...

..This work provides the first evidence of the importance of this gene family in the host-fungal interaction and virulence...

..albicans infections. gLUC59 and related cell surface-exposed luciferase reporters might find wide applications in molecular biology, cell biology, pathobiology, and high-throughput screens...

..The data suggest that multiple morphogenetic signaling pathways operate through the promoter of this adhesin gene to mediate its developmental regulation in this major fungal pathogen...

..CaGcn4 acts as a global regulator in C.albicans, co-ordinating both metabolic and morphogenetic responses to amino acid starvation...

..Therefore, pACT1-GFP provides a useful control for this quantitative GFP-based system in future analyses of C. albicans molecular responses during fungal infections...

..These data suggest that CaMsn4 and Mnl1 do not contribute significantly to stress responses in C. albicans. The data are consistent with the idea that stress signaling in this fungus has diverged significantly from that in budding yeast...

..Our comparison of the Gcn4 and Gcn2 regulons by transcript profiling reinforces the view that Gcn2 contributes to, but is not essential for, the activation of general amino acid control in C. albicans...

..Recommendations are made regarding the use of the metrics when reporting protein identification experiments...

..Reintegration of URA3 at an appropriate expression locus such as RPS10 can offset most problems related to the phenotypic changes associated with gene knockout methodologies...

..albicans. Therefore, the main role of Hsf1 in this pathogen might be the homeostatic modulation of chaperone levels in response to growth temperature, rather than the activation of acute responses to sudden thermal transitions...

..cerevisiae, but were not significantly induced in C. albicans. These differences presumably reflect the contrasting niches of these relatively benign and pathogenic yeasts, respectively...

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..albicans one-hybrid system. These observations are explained in models that are generally consistent with the Tup1-Ssn6 paradigm in budding yeast...

..Some of these functions are likely to contribute to the effects of Ace2 upon the virulence of C. glabrata...

..albicans. Using this one-hybrid system we have confirmed directly the positive and negative transcriptional activities of Nrg1 and Gcn4 in C. albicans...

..glabrata ace2 cells. Ace2 inactivation also resulted in the detection of new proteins in the C. glabrata secretome. The release of such proteins might contribute to the hypervirulence of ace2 cells...

..Our work defines a role for this YER130c orthologue in stress adaptation and cell death...

..This demonstrates the importance of N-glycan outer chain epitopes to the host-fungal interaction and virulence...

..albicans hyphae. The data support the hypothesis that cytoplasmic volume, rather than cell size, is critical for progression through G1...

..In contrast, the regulation of metabolic functions in response to very low glucose signals presumably ensures that yeast can exploit even minute amounts of this preferred nutrient...

..This system allows multiple and sequential genetic manipulations, which will facilitate the functional analysis of multigene families in C. albicans...

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..We concluded that recognition of C. albicans by monocytes/macrophages is mediated by 3 recognition systems of differing importance, each of which senses specific layers of the C. albicans cell wall...

..These make explicit what data might be most usefully captured about proteomics experiments and provide complementary routes toward the implementation of a proteome repository...

..Overall, the results suggest that Efh1p supports the regulatory functions of the primary regulator, Efg1p, and indicate a dual role for these APSES proteins in the regulation of fungal morphogenesis and metabolism...

..The CaAce2 protein is localized to the daughter nucleus of large budded cells at the end of mitosis. C. albicans Ace2p therefore plays a major role in morphogenesis and adherence and resembles S. cerevisiae Ace2p in function...

..These new vectors comprise a useful addition to the C. albicans molecular toolbox...

..Recent advances in unravelling the genomics of these species should facilitate efforts to achieve these goals. We discuss the contribution of genomics to the development of novel antifungals and new diagnostic tools...

..albicans and in the expression of genes encoding cell surface proteins during ER stress, factors that are important in virulence of this fungal pathogen...

..Therefore, N-oligosaccharide processing by ER glycosidases is required for cell wall integrity and for host-fungus interactions...

..Collectively, these results demonstrate functional similarities and differences between Als1p and Als3p, and suggest the potential for more complex interrelationships between the ALS genes and their encoded proteins...

..This niche specificity is reflected by the specific environmental conditions that drive the Hog1-regulated core stress response in C. albicans and by differences in the molecular circuitry that control this response...

..Our data suggest that C. glabrata perceives low pH as less stressful than higher pH. This contrasts with another opportunistic fungal pathogen of humans, Candida albicans...

..These results indicate a previously unsuspected and novel role for the GRE2 gene product as a suppressor of filamentation by virtue of encoding isovaleraldehyde reductase activity...

..These are the first B. poitrasii sequences to be reported. Based on CHS gene sequences, B. poitrasii chitin synthase genes place it with other zygomycetes on a fungal phylogenetic tree...