Donna M MacCallum

Donna M MacCallum
University of Aberdeen | ABDN · Institute of Medical Sciences

PhD Microbiology

About

241
Publications
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Introduction
Donna MacCallum is a Senior Lecturer in the School of Medical Sciences, University of Aberdeen and one of the Principle Investigators in the Aberdeen Fungal Group. Her research investigates host-fungal interactions during infection and disease, antifungal therapy and development of drug resistance. Donna MacCallum is expert in in vivo infection modelling and she also engages in 3Rs research.
Additional affiliations
January 2012 - present
January 2010 - December 2011
Newcastle University
January 2010 - present
Lausanne University Hospital

Publications

Publications (241)
Chapter
Animal colonizationColonization and infection modelsInfection models are frequently used to investigate host–pathogen interactions and disease progression. Here, we describe an effective model to investigate the ability of the newly emerged fungalFungal pathogen Candida aurisCandida auris to persistently colonize the gut of immunocompetent mice. In...
Article
Full-text available
Acquisition of the essential macronutrient phosphate is important for the virulence of Candida albicans , a major human fungal pathogen. All cells store phosphate as polyphosphate (polyP), which is rapidly mobilized when phosphate is limiting.
Article
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Monoclonal antibody (mAb)-based immunotherapies targeting systemic and deep-seated fungal infections are still in their early stages of development, with no licensed antifungal mAbs currently being available for patients at risk. The cell wall glycoproteins of Candida albicans are of particular interest as potential targets for therapeutic antibody...
Chapter
Candida auris can persist for long periods on hospital surfaces and on the skin. C. auris has the ability to form drug-resistant biofilms, which can substantially impact on patient outcome. In comparison to Candida albicans, C. auris has a lower capacity to form biofilms in in vitro models and a higher capacity when tested on animal skin models. In...
Preprint
MAb based immunotherapies targeting systemic and deep-seated fungal infections are still in their early stages of development with currently no licensed antifungal mAbs available. The cell wall glycoproteins of Candida albicans are potential targets for therapeutic antibody generation due to their extracellular location and key involvement in funga...
Article
An increasing number of outbreaks due to resistant non-albicans Candida species have been reported worldwide. Between 2014-2016, Candida isolates causing invasive candidiasis were recovered in a Mexican hospital. Isolates were identified to species level and antifungal susceptibility determined. In the time period studied, seventy-four invasive can...
Article
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Malassezia species are a major part of the normal mycobiota and colonise mainly sebum-rich skin regions of the body. This group of fungi cause a variety of infections such as pityriasis versicolour, folliculitis and fungaemia. In particular, Malassezia sympodialis and its allergens have been associated with non-infective inflammatory diseases such...
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Amino acid metabolism is crucial for fungal growth and development. Ureohydrolases produce amines when acting on l -arginine, agmatine, and guanidinobutyrate (GB), and these enzymes generate ornithine (by arginase), putrescine (by agmatinase), or GABA (by 4-guanidinobutyrase or GBase). Candida albicans can metabolize and grow on arginine, agmatine,...
Preprint
Full-text available
Malassezia species are a major part of the normal mycobiota and colonise mainly sebum-rich skin regions of the body. This group of fungi cause a variety of infections such as pityriasis versicolour, folliculitis and fungaemia. In particular, Malassezia sympodialis and its allergens have been associated with non-infective inflammatory diseases such...
Article
Full-text available
Candida auris is an emerging pathogenic yeast of significant clinical concern because of its frequent intrinsic resistance to fluconazole and often other antifungal drugs and the high mortality rates associated with systemic infections. Furthermore, C. auris has a propensity for persistence and transmission in health care environments. The reasons...
Article
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Human skin fungal infections (SFIs) affect 25% of the world's population. Most of these infections are superficial. The main limitation of current animal models of human superficial SFIs is that clinical presentation is different between the different species and animal models do not accurately reflect the human skin environment. An ex vivo human s...
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Traditional in vivo investigation of fungal infection and new antifungal therapies in mouse models is usually carried out using post mortem methodologies. However, biomedical imaging techniques focusing on non-invasive techniques using bioluminescent and fluorescent proteins have become valuable tools. These new techniques address ethical concerns...
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Current approaches to tackling fungal infections are limited, and new targets must be identified to protect against the emergence of resistant strains. We investigated the potential of targeting mitochondria, which are organelles required for energy production, growth, and virulence, in the human fungal pathogen Candida albicans . Our findings sugg...
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The original version of this Article contained errors in the author affiliations. Please see the associated correction for the full list of errors. These errors have been corrected in both the PDF and HTML versions of the Article.
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The high global burden of over one million annual lethal fungal infections reflects a lack of protective vaccines, late diagnosis and inadequate chemotherapy. Here, we have generated a unique set of fully human anti-Candida monoclonal antibodies (mAbs) with diagnostic and therapeutic potential by expressing recombinant antibodies from genes cloned...
Conference Paper
Background/Objectives: Children and young people with a cancer diagnosis are at risk of invasive fungal disease. The risk of fungal blood stream infections is increased if a long‐term vascular access device is present. We have demonstrated the utility of a human skin explant model for the study of, in the first instance, invasive candidiasis in the...
Preprint
Full-text available
The human fungal pathogen Candida albicans possesses two genes expressing a cyanide-insensitive Alternative Oxidase (Aox) enzymes in addition to classical and parallel electron transfer chains (ETC). In this study, we examine the role of Aox in C. albicans under conditions of respiratory stress, which may be inflicted during its interaction with th...
Conference Paper
Objective: To describe the immune response and biological processes during infection by F. solani using an ex-vivo human skin model Methods: An ex-vivo model was set up using breast and abdominal skin explants incubated at 37 ◦ C and 5% CO2 in Dul- becco’s Modified Enriched Medium (DMEM) supplemented with heat inactivated foetal calf serum and 1% p...
Preprint
Full-text available
The human fungal pathogen C. albicans requires respiratory function for normal growth, morphogenesis and virulence. As such the mitochondria represent an enticing target for the development of new antifungal strategies. This possibility is further bolstered by the presence of fungal specific characteristics. However, respiration in C. albicans , as...
Article
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Fungal cells change shape in response to environmental stimuli, and these morphogenic transitions drive pathogenesis and niche adaptation. For example, dimorphic fungi switch between yeast and hyphae in response to changing temperature. The basidiomycete Cryptococcus neoformans undergoes an unusual morphogenetic transition in the host lung from hap...
Data
Characterization of Titan cells. A) H99 was pre-grown in YNB + Glucose overnight at 150 RPM, 30°C and inoculated at OD600 = 0.5 and 0.01 into 10% FCS. Representative cells are shown after 7 days. Cells were fixed, permeabilised, and stained (DAPI, 300 ng/ml) to visualize nuclei. Scale bar = 20 μm. Imaged on a Zeiss Axio Observer Z1 at 40x. B) Repre...
Data
Flow cytometry showing cell size and DNA content of representative isolates. Individual isolates shown in Fig 3E are further analysed for cell size and DNA content, A) (i) Proportion of cells showing haploid DNA content (gate C1) for each isolate relative to a haploid control (H99); (ii) Size (FSC) and complexity (SSC) of total cell populations for...
Data
Histology of H99 infected mice and serum fractionation by SEC. A) Histology from untreated and Pen/Strep (2,000 U/L) treated H99 infected mice, and resulting lung fungal and bacterial CFUs. B) H99 untreated and Pen/Strep (2000 U/L) treated cells were induced for 24 hr to form Titan cells and degree and size of Titanisation were quantified (n>150; m...
Data
Titanisation and in vivo clinical and environmental isolates. A) Cryptococcus gattii strain R265 was pre-grown in YNB, inoculated into 10%FCS at OD = 0.01, and incubated at 37°C, 5%CO2 for 5 days. Cells were counterstained with India ink to reveal capsule. Scale bar = 10 μm. B) 63 Clinical and environmental isolates were induced for Titan cells (YN...
Data
Strains used in this study. (PDF)
Article
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Stress-activated protein kinase (SAPK) pathways are evolutionarily conserved eukaryotic signalling modules that are essential for the virulence of human pathogenic fungi. The Hog1 SAPK in Candida albicans is robustly phosphorylated in response to a number of host-imposed stresses, and is essential for virulence. The current dogma is that stress-ind...
Preprint
Fungi undergo changes in cell shape in response to environmental stimuli that drive pathogenesis and niche adaptation, such as the yeast-to-hyphal transition of dimorphic fungi in response to changing temperature. The basidiomycete Cryptococcus neoformans undergoes an unusual morphogenetic transition in the host lung from haploid yeast to large, hi...
Article
Full-text available
The pathogenic yeast Candida albicans faces multiple challenges within its human host. These include the need to protect itself against the toxic oxidants used by the host to kill invading microbes, and the need to scavenge iron, an essential micronutrient that is limiting in certain tissues. The iron-containing enzyme, catalase, detoxifies hydroge...
Article
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Candida albicans is able to proliferate in environments that vary dramatically in ambient pH, a trait required for colonising niches such as the stomach, vaginal mucosal and the GI tract. Here we show that growth in acidic environments involves cell wall remodelling which results in enhanced chitin and β-glucan exposure at the cell wall periphery....
Data
Stress resistance of C. albicans tetON-CAT1 and ACT1-CAT1 strains. C. albicans cultures were pre-grown in YPD with 20 μM doxycycline, dilutions spotted onto YPD plates containing H2O2 and/or NaCl stresses at the specified concentrations, and photographed after 24 h growth at 30°C: CAT1/CAT1, Ca674; CAT1/cat1Δ, Ca1862; cat1Δ/cat1Δ, Ca1864; ACT1p-CAT...
Data
Gating strategy for the analysis of C. albicans Cat1-GFP expressing cells. Exponential populations of C. albicans CAT1-GFP cells (Ca2213: S1 Table) growing in YPD at 30°C were subjected to fluorescence activated cell sorting. (A) First, singlets were selected and doublets excluded by analysing the FSC signals height versus area. (B) Next, cells of...
Data
Iron suppresses the fitness defect of doxycycline-treated tetON-CAT1 C. albicans cells. (A) Iron supplementation restores the growth of doxycycline-treated tetON-CAT1 C. albicans cells to normal, while reducing the growth of wild type and cat1Δ null cells. The growth of new C. albicans isolates was monitored (OD600) in YPD containing 0 or 20 μM dox...
Data
Analysis of C. albicans ACT1-GFP expressing cells. Exponential C. albicans ACT1-GFP cells (Ca230: S1 Table) were grown in the same way as for S2 Fig, and then subjected to fluorescence activated cell sorting, as before. (A) Singlets were selected and doublets excluded by analysing the FSC signals height versus area. (B) Cells of similar size were t...
Data
Loss of phenotype in some tetON-CAT1 isolates. TetON-CAT1 isolates 1, 4 and 10 (Ca2038, Ca2041, Ca2044: S1 Table) behaved differently in vivo: isolate 1 displayed decreased colonisation in certain tissues (Fig 5), whereas isolates 4 and 10 did not (see text). Therefore, we tested whether isolates 4 and 10 had lost their phenotype over time. To achi...
Data
Release of the outer phosphomannan does not result in unmasking of inner cell wall components. C. albicans strains were grown to mid-log phase in YPD and YPD buffered at pH4, fixed with 4% PFA and carbohydrate exposure quantified by immunofluorescence. Fluorescence was quantified by FACS analysis of 10,000 events per strain, per condition, per repe...
Data
De-cloaking of the fungal cell wall in response to environmental pH is an active process. C. albicans cells were grown overnight in YPD. Cells were killed by fixing with 4% PFA, heat killing at 65°C for 2 h, treatment with 1 J UV light, or 100 mM thimerosal for 45 mins. Cells were washed and incubated in YPD buffered at pH2, 4 and 6 for 4 h. Cells...
Data
C. albicans strains used in this study. (DOCX)
Data
Unmasking of β-glucan in response to environmental pH is not mediated via conventional cell wall or pH sensing pathways. a) β-glucan unmasking in kinase mutants grown to mid-log phase in YPD buffered to pH4 as quantified by FACS analysis of immunofluorescent staining and repressed as fold change relative to YPD. Data represent the mean ± SEM from t...
Data
The rim101Δ and bcr1Δ mutants display reduced phagocytosis. C. albicans strains were grown in YPD at the appropriate pH to mid-log phase, co-incubated with J774.1A macrophages at an MOI = 5 for 1 h and the a) phagocytosis index and b) association index determined. Data represent the mean ± SEM from three independent repeats. c) PBMCs were incubated...
Article
Full-text available
IMPORTANCE The availability and metabolism of amino acids are increasingly recognized as crucial regulators of immune functions. In acute infections, the conversion of the “conditionally essential” amino acid l-arginine by the inducible nitric oxide synthase to nitric oxide is a resistance factor that is produced by the host to fight pathogens. Man...
Article
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The Ypd1 phosphorelay protein is a central constituent of fungal two-component signal transduction pathways. Inhibition of Ypd1 in Saccharomyces cerevisiae and Cryptococcus neoformans is lethal due to the sustained activation of the 'p38-related' Hog1 stress-activated protein kinase (SAPK). As two-component signalling proteins are not found in anim...
Data
Effect of deleting Hog1, or Hog1 and Ypd1, on experimental infection outcome. Infection with either hog1Δ or hog1Δ ypd1Δ cells resulted in weight increases, lower kidney fungal burdens and, thus, lower outcome scores compared to that observed with wild-type cells. Statistical analysis revealed that for all parameters; weight loss, kidney fungal bur...
Data
Oligonucleotides used in this study. (DOCX)
Data
Doxycycline does not stimulate Hog1 phosphorylation. The indicated strains were treated or not with 20μg/ml doxycycline (DOX) for 1 h, and cell extracts were analysed for phosphorylated Hog1 by western blotting. Blots were probed for phosphorylated Hog1 (Hog1-P), stripped and reprobed for total Hog1 (Hog1). Hog1 phosphorylation is stimulated upon d...
Data
Doxycycline treatment does not affect rate of uptake of C. albicans tetO-YPD1 cells. (A) Percentage uptake of tetOYPD1 cells grown in the presence (+DOX) or absence (-DOX) of doxycycline. No significant difference between uptake events + or − minus Dox by J774.1 macrophages after 6h co incubation was detected. (B) Engulfment time required for the i...
Data
HOG1 is regulated differently at the RPS10 locus in response to sustained Hog1 activation. (A) Hog1 phosphorylation is not sustained in hog1Δypd1Δ+HOG1 cells over time and this is accompanied by a reduction in total Hog1 protein levels. Western blot analysis of whole cell extracts isolated from exponentially growing hog1Δ+HOG1 (JC52) and hog1Δypd1Δ...
Data
Doxycycline treatment does not affect C. albicans virulence in a murine infection model. Kidney fungal burden measurements, percentage weight loss, and outcome score measurements of mice infected with wild-type C. albicans cells (SC5314) and administered doxycycline (+DOX) or not (-DOX). Comparison of +DOX and -DOX treated groups by Kruskal-Wallis...
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Doxycycline treatment does not affect C. albicans virulence in a C. elegans model of infection. Nematodes were infected with wild-type THE1 or wild-type JC806 cells and transferred to liquid medium either with (+DOX) or without (-DOX) doxycycline. Doxycycline had no significant impact on nematode killing infected with either wild-type strain in (P>...
Article
Full-text available
As they proliferate, fungi expose antigens at their cell surface that are potent stimulators of the innate immune response, and yet the commensal fungus Candida albicans is able to colonize immuno competent individuals. We show that C. albicans may evade immune detection by presenting a moving immunological target. We report that the exposure of β-...
Article
Full-text available
Filamentous growth is a hallmark of C. albicans pathogenicity compared to less-virulent ascomycetes. A multitude of transcription factors regulate filamentous growth in response to specific environmental cues. Our work, however, suggests the evolutionary history of C. albicans that resulted in its filamentous growth plasticity may be tied to a chan...
Data
CdTlo1p is unstable, compared to CaTloα12p, when over-expressed in C. albicans. (A) Immunoblot showing that HA-tagged CdTlo1p (yLM390) levels are lower than CaTloα12p (yLM389) levels when expressed from the same strong promoter (pACT1) in C. albicans. Two independent transformants (‘1’ and ‘2’) were tested and compared with two independent C. albic...
Data
Non-Mediator associated CdTlo1 protein has a short half-life compared to CaTloα12p. (A) Immunoblot of endogenous HA-tagged CdTlo1p in a wild type C. dubliniensis strain (yLM301) after treatment with cycloheximide (CHX). Coomassie blue staining (CBS) was used as a loading control. (B) Immunoblot of endogenous HA-tagged CaTloα34 in a wild type C. alb...
Data
Non-Mediator associated CdTlo1 protein has a short half-life compared to CaTloα12p. (A) Immunoblot of overexpressed HA-tagged CaTloα12p in a wild type C. albicans strain (yLM393) after treatment with cycloheximide (CHX). Coomassie blue staining (CBS) was used as a loading control. (B) Immunoblot of overexpressed HA-tagged CdTlo1p in a wild type C....
Data
CaTloα12 ‘Helix 3’, but not the C-terminal TAD, is required for its stability when overexpressed in a C. dubliniensis tloΔ/Δ strain. (A) Immunoblot showing over-expression of HA-tagged CaTLOα12, CdTLO1, and CaTLOα12/CdTLO1 chimeras from the TDH3 promoter in a C. dubliniensis tloΔ/Δ strain. Strains used to generate the data are yLM303(CaTLOα12), yLM...
Data
Analysis of affinity purified 6His-3Flag tagged CaTloα12/CdTlo1 chimeric proteins demonstrates ‘Helix 2’ of CdTlo1 is required for stable incorporation of chimeric Tlo proteins into C. dubliniensis Mediator. Immunoblot analysis of cell lysate, heparin purified, and Flag-purified samples derived from a C. dubliniensis tloΔ/Δ strain over expressing 6...
Data
The C. dubliniensis agar invasion and embedded agar filamentation phenotypes are also observed when CdTLO2 overexpression is driven by the CaACT1 and CdENO1 promoters in Wü284 and additional C. dubliniensis strain backgrounds. (A) Embedded agar filamentation (two left columns) and agar invasion (two right columns) phenotype analysis with one copy o...
Data
Nuclear localization of the over-expressed transcriptional activation domain of CdTlo2 in a tlo1Δ/Δ C. dubliniensis strain, by fusion of a NLS to its N-terminus, facilitates embedded agar and agar invasion phenotypes. (A) TLO constructs, which were N-terminally fused with NLS-GFP sequence and C-terminally HA-tagged, were over-expressed from a TDH3...
Data
‘SW’ colonies do not exhibit a greater degree of CdTlo2 nuclear localization than ‘smooth’ colonies, when a GFP-CdTLO2 construct is overexpressed in C. dubliniensis. CdTLO2, which was N-terminally tagged with a GFP sequence and C-terminally HA-tagged, was overexpressed from a TDH3 promoter in a wild type (Wü284) C. dubliniensis strain, and produced...
Data
List of C. albicans strains used in this study. (PDF)
Data
Deletion of MED3 does not change CdTLO1 mRNA level in C. dubliniensis. Liquid culture of two independent colonies (‘1’ and ‘2’) from TLO1 C-terminal HA tagged wild type (yLM301) and med3 null (yLM308) C. dubliniensis strains were grown and the RNA extracted. The steady state ratio of TLO1 mRNA levels to ACT1 mRNA was determined by RT-qPCR and norma...
Data
CdTlo2 overexpression isolates possessing the super wrinkled (SW) phenotype have 4 or more copies of the pTDH3-CdTLO2 construct. (A) Radar plot shows extra copies of TLO2-HA ORF and SAT1 ORF are present in 3 independent ‘SW’ (yLM343) isolates compared with an isolate of their smooth (yLM339) counterpart when wild type C. dubliniensis (Wü284) is tra...