Publications by authors named "Poppy Sephton-Clark"

Candida auris is a growing concern due to its resistance to antifungal drugs, particularly amphotericin B (AMB), detected in 30 to 60% of clinical isolates. However, the mechanisms of AMB resistance remain poorly understood. Here we investigated 441 in vitro- and in vivo-evolved C.

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  • Cryptococcal meningitis is a major cause of death in people with HIV/AIDS, but there's still a limited understanding of how the fungus changes during infection.
  • A study analyzed the whole genomes of 372 clinical isolates from patients in Malawi and Cameroon, revealing that Cameroonian isolates are more genetically uniform compared to their Malawian counterparts, and show different rates of mutations in key genes.
  • Longitudinal samples taken from patients in Cameroon highlighted genetic changes during infection and revealed mixed infections in 13% of patients, showcasing the evolutionary dynamics of the fungus in this context.
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Talaromycosis, a severe and invasive fungal infection caused by Talaromyces marneffei, is difficult to treat and impacts those living in endemic regions of Southeast Asia, India, and China. While 30% of infections result in mortality, our understanding of the genetic basis of pathogenesis for this fungus is limited. To address this, we apply population genomics and genome-wide association study approaches to a cohort of 336 T.

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  • * Researchers analyzed 336 fungal isolates from a clinical trial in Vietnam, discovering distinct genetic clades linked to disease severity and instances of relapse due to multi-strain infections.
  • * The study highlights specific genetic variants associated with patient outcomes, showing how pathogen genetics affects disease progression and identifying rapid evolutionary responses to external pressures.
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A pet cockatoo was the suspected source of recovered from an immunocompromised patient with cryptococcosis based on molecular analyses available in 2000. Here, we report whole genome sequence analysis of the clinical and cockatoo strains. Both are closely related MATα strains belonging to the VNII lineage, confirming that the human infection likely originated from pet bird exposure.

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  • Cryptococcus neoformans causes cryptococcosis, which leads to around 180,000 deaths annually, particularly affecting patients with HIV, highlighting a need to understand the link between genetic diversity of the fungus and clinical outcomes.
  • A genome-wide association study (GWAS) of 284 C. neoformans isolates from Malawi reveals variants associated with fungal growth rates and burdens, with significant variations in genes related to metabolism and growth.
  • The findings demonstrate that glycolysis is crucial for the fungus's survival in the central nervous system and may influence patient mortality, suggesting that understanding these genetic factors can improve treatment outcomes for cryptococcosis.
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Unlabelled: Invasive fungal infections are increasingly common and carry high morbidity and mortality, yet fungal diagnostics lag behind bacterial diagnostics in rapidly identifying the causal pathogen. We previously devised a fluorescent hybridization-based assay to identify bacteria within hours directly from blood culture bottles without subculture, called phylogeny-informed rRNA-based strain identification (Phirst-ID). Here, we adapt this approach to unambiguously identify 11 common pathogenic Candida species, including C.

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Opportunistic infections by environmental fungi are a growing clinical problem, driven by an increasing population of people with immunocompromising conditions. Spores of the Mucorales order are ubiquitous in the environment but can also cause acute invasive infections in humans through germination and evasion of the mammalian host immune system. How they achieve this and the evolutionary drivers underlying the acquisition of virulence mechanisms are poorly understood.

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  • Cryptococcus neoformans is a dangerous fungal pathogen that can significantly affect the human central nervous system, leading to high rates of illness and death, especially in patients with cryptococcal meningoencephalitis.
  • This research involved analyzing yeast transcriptomes from patient cerebrospinal fluid samples to understand the genetic behaviors of C. neoformans and Cryptococcus gattii in various environments.
  • Key findings included the identification of genes important for survival and virulence, with particular emphasis on carbon metabolism and stress responses, leading to the discovery of a glycoprotein gene that impacts the virulence of these fungi in animal models.
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is an invasive fungal pathogen responsible for the frequently fatal disease mucormycosis. Germination, a crucial mechanism by which infectious spores of cause disease, is a key developmental process that transforms the dormant spore state into a vegetative one. The molecular mechanisms that underpin this transformation may be key to controlling mucormycosis; however, the regulation of germination remains poorly understood.

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Fungi, algae, plants, protozoa, and bacteria are all known to form spores, especially hardy and ubiquitous propagation structures that are also often the infectious agents of diseases. Spores can survive for thousands of years, frozen in the permafrost (Kochkina et al., 2012), with the oldest viable spores extracted after 250 million years from salt crystals (Vreeland, Rosenzweig, & Powers, 2000).

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Vomocytosis, or nonlytic extrusion, is a poorly understood process through which macrophages release live pathogens that they have failed to kill back into the extracellular environment. Vomocytosis is conserved across vertebrates and occurs with a diverse range of pathogens, but to date, the host signaling events that underpin expulsion remain entirely unknown. We use a targeted inhibitor screen to identify the MAP kinase ERK5 as a critical suppressor of vomocytosis.

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