A5019397456- Antifungal resistance and susceptibility
- Fungal Infections and Studies
- Plant Pathogens and Fungal Diseases
- Plant-Microbe Interactions and Immunity
- Nail Diseases and Treatments
- Infectious Diseases and Mycology
- Insect symbiosis and bacterial influences
- Trace Elements in Health
- Fungal and yeast genetics research
- Gut microbiota and health
- Fungal Biology and Applications
- Studies on Chitinases and Chitosanases
- Pneumocystis jirovecii pneumonia detection and treatment
- Plant Pathogens and Resistance
- Mycobacterium research and diagnosis
- Plant Disease Resistance and Genetics
- Antimicrobial Peptides and Activities
- Invertebrate Immune Response Mechanisms
- Genomics and Phylogenetic Studies
- Heavy Metal Exposure and Toxicity
- Trypanosoma species research and implications
- bioluminescence and chemiluminescence research
- Diversity and Career in Medicine
- Sex and Gender in Healthcare
- Medicinal Plants and Neuroprotection
University of Birmingham
2017-2025
Medical Research Council
2018-2024
University of Exeter
2022-2024
University of Sheffield
2023
University of Aberdeen
2013-2018
Duke University
2008-2013
Duke University Hospital
2008-2011
Duke Medical Center
2008
Candida albicans is able to proliferate in environments that vary dramatically ambient pH, a trait required for colonising niches such as the stomach, vaginal mucosal and GI tract. Here we show growth acidic involves cell wall remodelling which results enhanced chitin β-glucan exposure at periphery. Unmasking of underlying immuno-stimulatory innate immune recognition C. by macrophages neutrophils, induced stronger proinflammatory cytokine response, driven through C-type lectin-like receptor,...
Fungal cells change shape in response to environmental stimuli, and these morphogenic transitions drive pathogenesis niche adaptation. For example, dimorphic fungi switch between yeast hyphae changing temperature. The basidiomycete Cryptococcus neoformans undergoes an unusual morphogenetic transition the host lung from haploid large, highly polyploid termed Titan cells. influence fungal interaction with cells, including through increased drug resistance, altered cell size, Pathogen...
ABSTRACT Candida albicans is a major life-threatening human fungal pathogen in the immunocompromised host. Host defense against systemic infection relies heavily on capacity of professional phagocytes innate immune system to ingest and destroy cells. A number pathogens, including C. , have evolved mechanisms that attenuate efficiency phagosome-mediated inactivation, promoting their survival replication within Here we visualize host-pathogen interactions using live-cell imaging show viable,...
The titan cell is a recently described morphological form of the pathogenic fungus Cryptococcus neoformans. Occurring during earliest stages lung infection, cells are 5 to 10 times larger than normal yeast-like cells, thereby resisting engulfment by phagocytes and favoring persistence infection. These enlarged exhibit an altered capsule structure, thickened wall, increased ploidy, resistance nitrosative oxidative stresses. We demonstrate that two G-protein-coupled receptors important for...
ABSTRACT Cryptococcus neoformans causes lethal meningitis and accounts for approximately 10%–15% of AIDS-associated deaths worldwide. There are major gaps in our understanding how this fungus invades the mammalian brain. To investigate dynamics C. tissue invasion, we mapped fungal localization host cell interactions infected brain, lung, upper airways using mouse models systemic airway infection. enable this, developed an situ imaging pipeline capable measuring large volumes while preserving...
Efficient carbon assimilation is critical for microbial growth and pathogenesis. The environmental yeast Saccharomyces cerevisiae "Crabtree positive", displaying a rapid metabolic switch from the of alternative sources to sugars. Following exposure sugars, this mediated by transcriptional repression genes (carbon catabolite repression) turnover (catabolite inactivation) enzymes involved in sources. pathogenic Candida albicans Crabtree negative. It has retained mechanisms, but undergone...
Nutritional immunity describes the host-driven manipulation of essential micronutrients, including iron, zinc and manganese. To withstand nutritional proliferate within their hosts, pathogenic microbes must express efficient micronutrient uptake homeostatic systems. Here we have elucidated pathway cellular assimilation in major human fungal pathogen Candida albicans. Bioinformatics analysis identified nine putative transporters: four cytoplasmic-import Zip proteins (Zrt1, Zrt2, Zrt3...
Opportunistic infections by environmental fungi are a growing clinical problem, driven an increasing population of people with immunocompromising conditions. Spores the Mucorales order ubiquitous in environment but can also cause acute invasive humans through germination and evasion mammalian host immune system. How they achieve this evolutionary drivers underlying acquisition virulence mechanisms poorly understood. Here, we show that isolate Rhizopus microsporus contains Ralstonia pickettii...
Nutritional immunity is a process whereby an infected host manipulates essential micronutrients to defend against invading pathogen. We reveal dynamic aspect of nutritional during infection that involves copper assimilation. Using combination laser ablation inductively coupled mass spectrometry (LA-ICP MS) and metal mapping, immunohistochemistry, gene expression profiling from tissues, we show readjustments in hepatic, splenic renal homeostasis accompany disseminated Candida albicans...
In the human fungal pathogen Cryptococcus neoformans, Ras signaling mediates sexual differentiation, morphogenesis, and pathogenesis. By studying prenylation palmitoylation in this organism, we have found that subcellular localization of protein dictates its downstream specificity. Inhibiting C. neoformans Ras1 results defective general membrane targeting loss all function. contrast, to plasma is required for normal morphogenesis survival at high temperatures. However, are not Ras-dependent...
Abstract Microglia provide protection against a range of brain infections including bacteria, viruses and parasites, but how these glial cells respond to fungal is poorly understood. We investigated the role microglia in context cryptococcal meningitis, most common cause meningitis humans. Using series transgenic- chemical-based depletion methods we found that, contrary their protective during other infections, loss did not affect control Cryptococcus neoformans infection which was...
Fungi can intervene in hosts’ brain function. In humans, they drive neuroinflammation, neurodegenerative diseases and psychiatric disorders. However, how fungi alter the host is unknown. The mechanism underlying innate immunity to well-known universally conserved downstream of shared Toll/TLR receptors, which via adaptor MyD88 transcription factor Dif/NFκB, induce expression antimicrobial peptides (AMPs). brain, Toll-1 could also an alternative pathway Sarm, causes cell death instead. Sarm...
The precise regulation of morphogenesis is a key mechanism by which cells respond to variety stresses, including those encountered microbial pathogens in the host. polarity protein Cdc42 regulates cellular throughout eukaryotes, and we explore role proteins host survival human fungal pathogen Cryptococcus neoformans. Uniquely, C. neoformans has two functional paralogues, Cdc420. Here investigate contribution each paralogue resistance stress. In contrast non-pathogenic model organisms, are...
Precise genome modification is essential for the molecular dissection of Candida albicans, and yielding invaluable information about roles specific gene functions in this major fungal pathogen humans. C. albicans naturally diploid, unable to undergo meiosis, utilizes a non-canonical genetic code. Hence, specialized tools have had be developed disruption that permit deletion both target alleles, some cases, recycling Candida-specific selectable markers. Previously, we tool based on Cre...
Proliferation and morphogenesis in eukaryotic cells depend on the concerted activity of Rho-type GTPases, including Ras, Cdc42, Rac. The sexually dimorphic fungus Cryptococcus neoformans, which encodes paralogous, non-essential copies all three, provides a unique model to examine interactions these conserved proteins. Previously, we demonstrated that RAS1 mediates C. neoformans virulence by acting as central regulator both thermotolerance mating. We report here ras1Δ mutants accumulate...
During infection, the human fungal pathogen Cryptococcus neoformans undergoes an unusual change in size, from small haploid yeast to large polyploid Titan cells. This transition is now well recognized as a virulence factor, but significant questions remain about how Titanisation regulated and it influences disease progression. Progress has been impeded by lack of vitro model for yeast-to-Titan transition, challenge that was recently overcome three independent groups. Here, we review...