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Search Results: 1 - 10 of 401636 matches for " Donna M. MacCallum "
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Hosting Infection: Experimental Models to Assay Candida Virulence
Donna M. MacCallum
International Journal of Microbiology , 2012, DOI: 10.1155/2012/363764
Abstract: Although normally commensals in humans, Candida albicans, Candida tropicalis, Candida parapsilosis, Candida glabrata, and Candida krusei are capable of causing opportunistic infections in individuals with altered physiological and/or immunological responses. These fungal species are linked with a variety of infections, including oral, vaginal, gastrointestinal, and systemic infections, with C. albicans the major cause of infection. To assess the ability of different Candida species and strains to cause infection and disease requires the use of experimental infection models. This paper discusses the mucosal and systemic models of infection available to assay Candida virulence and gives examples of some of the knowledge that has been gained to date from these models.
Hosting Infection: Experimental Models to Assay Candida Virulence
Donna M. MacCallum
International Journal of Microbiology , 2012, DOI: 10.1155/2012/363764
Abstract: Although normally commensals in humans, Candida albicans, Candida tropicalis, Candida parapsilosis, Candida glabrata, and Candida krusei are capable of causing opportunistic infections in individuals with altered physiological and/or immunological responses. These fungal species are linked with a variety of infections, including oral, vaginal, gastrointestinal, and systemic infections, with C. albicans the major cause of infection. To assess the ability of different Candida species and strains to cause infection and disease requires the use of experimental infection models. This paper discusses the mucosal and systemic models of infection available to assay Candida virulence and gives examples of some of the knowledge that has been gained to date from these models. 1. Candida and Man 1.1. Carriage of Candida Species In healthy individuals Candida species are harmless members of the normal gastrointestinal (GI), oral, and vaginal microbial flora. It is assumed that everyone carries Candida in their GI tract (reviewed in [1]), with C. albicans the species most frequently identified in faecal sampling, representing 40–70% of isolates [2–4]. Other isolates are usually identified as C. parapsilosis, C. glabrata, C. tropicalis, or C. krusei [2–4]. In comparison to GI carriage, oral carriage is observed in only ~40% of healthy individuals, with considerable variation found between studies (reviewed in [1]). Higher carriage levels are generally associated with diabetes, cancer, HIV, or denture use (reviewed in [1]). Again, the majority of isolates (~80%) are identified as C. albicans, with C. glabrata or C. parapsilosis making up the remainder [5–9]. Vaginal carriage occurs in an even smaller proportion of the healthy population, with only ~20% of healthy women found to have vaginal Candida carriage [10–13]. C. albicans is again the most commonly identified species, with C. glabrata the only other species usually found [10, 12, 14–17]. Therefore, C. albicans is the major species found as a commensal in healthy individuals, with four other species, C. tropicalis, C. parapsilosis, C. glabrata, and C. krusei, also found. 1.2. Candida and Disease Candida species, however, have an alternative lifestyle, causing opportunistic infection in hosts with altered physiological or immune response. The infections caused by Candida species range from self-limiting, superficial mucosal lesions (commonly referred to as thrush), chronic and/or recurrent mucosal, skin, and nail infections, through to life-threatening invasive or disseminated infection [1, 18–21]. In humans, the
Early-Expressed Chemokines Predict Kidney Immunopathology in Experimental Disseminated Candida albicans Infections
Donna M. MacCallum, Luis Castillo, Alistair J. P. Brown, Neil A. R. Gow, Frank C. Odds
PLOS ONE , 2009, DOI: 10.1371/journal.pone.0006420
Abstract: Background The mouse intravenous challenge model of Candida albicans infection is widely used to determine aspects of host-fungus interaction. We investigated the production of cytokines in the kidneys and spleen of animals up to 48 h after challenge with virulent and attenuated isolates and related these responses to semi-quantitative estimations of histopathological changes in the kidney. Methodology/Principal Findings Progression of Candida albicans infection of the kidney in response to highly virulent fungal strains was characterized by higher levels of host cellular infiltrate, higher lesion densities and greater quantities of fungal elements at 24 and 48 h, and by higher kidney concentrations of IL-1β, MCP-1, KC, IL-6, G-CSF, TNF, MIP-2 and MIP-1β, among the immune effectors measured. Levels of the chemokine KC as early as 12 h after challenge correlated significantly with all later measurements of lesion severity. Early renal IL-6 and MIP-1β concentrations also correlated with subsequent damage levels, but less significantly than for KC. All chemokines tested appeared in kidney homogenates, while most of the cytokines were undetectable in kidney and spleen homogenates. GM-CSF and IL-10 showed inverse correlations with measures of lesion severity, suggesting these alone may have exerted a defensive role. Spleen levels of KC at all times showed significant associations with kidney lesion measurements. Conclusions/Significance Elevated chemokine levels, including KC, represent the earliest responses to C. albicans infection in the mouse kidney. Fungal strains of low mouse virulence stimulate a lower innate response and less host infiltrate than more virulent strains. These findings are consistent with immunopathological damage to kidneys in the mouse C. albicans infection model and with growing evidence implicating some TLR pathways as the main point of interaction between fungal surface polysaccharides and leukocytes.
Identification of a Novel Response Regulator, Crr1, That Is Required for Hydrogen Peroxide Resistance in Candida albicans
Catherine R. Bruce, Deborah A. Smith, David Rodgers, Alessandra da Silva Dantas, Donna M. MacCallum, Brian A. Morgan, Janet Quinn
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0027979
Abstract: Candida albicans colonises numerous niches within humans and thus its success as a pathogen is dependent on its ability to adapt to diverse growth environments within the host. Two component signal transduction is a common mechanism by which bacteria respond to environmental stimuli and, although less common, two component-related pathways have also been characterised in fungi. Here we report the identification and characterisation of a novel two component response regulator protein in C. albicans which we have named CRR1 (Candida Response Regulator 1). Crr1 contains a receiver domain characteristic of response regulator proteins, including the conserved aspartate that receives phosphate from an upstream histidine kinase. Significantly, orthologues of CRR1 are present only in fungi belonging to the Candida CTG clade. Deletion of the C. albicans CRR1 gene, or mutation of the predicted phospho-aspartate, causes increased sensitivity of cells to the oxidising agent hydrogen peroxide. Crr1 is present in both the cytoplasm and nucleus, and this localisation is unaffected by oxidative stress or mutation of the predicted phospho-aspartate. Furthermore, unlike the Ssk1 response regulator, Crr1 is not required for the hydrogen peroxide-induced activation of the Hog1 stress-activated protein kinase pathway, or for the virulence of C. albicans in a mouse model of systemic disease. Taken together, our data suggest that Crr1, a novel response regulator restricted to the Candida CTG clade, regulates the response of C. albicans cells to hydrogen peroxide in a Hog1-independent manner that requires the function of the conserved phospho-aspartate.
Fungal Iron Availability during Deep Seated Candidiasis Is Defined by a Complex Interplay Involving Systemic and Local Events
Joanna Potrykus,David Stead,Donna M. MacCallum,Dagmar S. Urgast,Andrea Raab,Nico van Rooijen,J?rg Feldmann,Alistair J. P. Brown
PLOS Pathogens , 2013, DOI: 10.1371/journal.ppat.1003676
Abstract: Nutritional immunity – the withholding of nutrients by the host – has long been recognised as an important factor that shapes bacterial-host interactions. However, the dynamics of nutrient availability within local host niches during fungal infection are poorly defined. We have combined laser ablation-inductively coupled plasma mass spectrometry (LA-ICP MS), MALDI imaging and immunohistochemistry with microtranscriptomics to examine iron homeostasis in the host and pathogen in the murine model of systemic candidiasis. Dramatic changes in the renal iron landscape occur during disease progression. The infection perturbs global iron homeostasis in the host leading to iron accumulation in the renal medulla. Paradoxically, this is accompanied by nutritional immunity in the renal cortex as iron exclusion zones emerge locally around fungal lesions. These exclusion zones correlate with immune infiltrates and haem oxygenase 1-expressing host cells. This local nutritional immunity decreases iron availability, leading to a switch in iron acquisition mechanisms within mature fungal lesions, as revealed by laser capture microdissection and qRT-PCR analyses. Therefore, a complex interplay of systemic and local events influences iron homeostasis and pathogen-host dynamics during disease progression.
CO2 Acts as a Signalling Molecule in Populations of the Fungal Pathogen Candida albicans
Rebecca A. Hall,Luisa De Sordi,Donna M. MacCallum,Hüsnü Topal,Rebecca Eaton,James W. Bloor,Gary K. Robinson,Lonny R. Levin,Jochen Buck,Yue Wang,Neil A. R. Gow,Clemens Steegborn,Fritz A. Mühlschlegel
PLOS Pathogens , 2010, DOI: 10.1371/journal.ppat.1001193
Abstract: When colonising host-niches or non-animated medical devices, individual cells of the fungal pathogen Candida albicans expand into significant biomasses. Here we show that within such biomasses, fungal metabolically generated CO2 acts as a communication molecule promoting the switch from yeast to filamentous growth essential for C. albicans pathology. We find that CO2-mediated intra-colony signalling involves the adenylyl cyclase protein (Cyr1p), a multi-sensor recently found to coordinate fungal responses to serum and bacterial peptidoglycan. We further identify Lys 1373 as essential for CO2/bicarbonate regulation of Cyr1p. Disruption of the CO2/bicarbonate receptor-site interferes selectively with C. albicans filamentation within fungal biomasses. Comparisons between the Drosophila melanogaster infection model and the mouse model of disseminated candidiasis, suggest that metabolic CO2 sensing may be important for initial colonisation and epithelial invasion. Our results reveal the existence of a gaseous Candida signalling pathway and its molecular mechanism and provide insights into an evolutionary conserved CO2-signalling system.
Anisotropic and inhomogeneous cosmologies
M. A. H. MacCallum
Physics , 1992,
Abstract: This review was given at the 65th birthday meeting of D.W. Sciama, The Renaissance of General Relativity and Cosmology, to be published by Cambridge University Press. It presents progress in the understanding of non-standard relativistic cosmologies during Sciama's career, organized by the areas of application rather than the mathematical types of the models.
Inhomogeneous and anisotropic cosmologies
M. A. H. MacCallum
Physics , 1992,
Abstract: This is a review of cosmological models prepared for the Pont d'Oye workshop on the origin of structure in the universe. The classes of models are discussed in turn, and then some of their uses are considered.
Hypersurface-orthogonal generators of an orthogonally transitive transitive $G_2I$, topological identifications, and axially and cylindrically symmetric spacetimes
M. A. H. MacCallum
Physics , 1997, DOI: 10.1023/A:1018833219068
Abstract: A criterion given by Castejon-Amenedo and MacCallum (1990) for the existence of (locally) hypersurface-orthogonal generators of an orthogonally-transitive two-parameter Abelian group of motions (a $G_2I$) in spacetime is re-expressed as a test for linear dependence with constant coefficients between the three components of the metric in the orbits in canonical coordinates. In general, it is shown that such a relation implies that the metric is locally diagonalizable in canonical coordinates, or has a null Killing vector, or can locally be written in a generalized form of the `windmill' solutions characterized by McIntosh. If the orbits of the $G_2I$ have cylindrical or toroidal topology and a periodic coordinate is used, these metric forms cannot in general be realized globally as they would conflict with the topological identification. The geometry then has additional essential parameters, which specify the topological identification. The physical significance of these parameters is shown by their appearance in global holonomy and by examples of exterior solutions where they have been related to characteristics of physical sources. These results lead to some remarks about the definition of cylindrical symmetry.
Milestones of general relativity: Hubble's law (1929) and the expansion of the universe
M. A. H. MacCallum
Physics , 2015, DOI: 10.1088/0264-9381/32/12/124002
Abstract: Hubble's announcement of the magnitude-redshift relation \cite{Hub29} brought about a major change in our understanding of the Universe. After tracing the pre-history of Hubble's work, and the hiatus in our understanding which his underestimate of distances led to, this review focuses on the development and success of our understanding of the expanding universe up to the present day, and the part which General Relativity plays in that success.
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