A5007747543- Fungal Infections and Studies
- Antifungal resistance and susceptibility
- Neonatal Respiratory Health Research
- Nail Diseases and Treatments
- Plant Pathogens and Fungal Diseases
- Immune Response and Inflammation
- Toxin Mechanisms and Immunotoxins
- Neuroscience of respiration and sleep
- Plant-Microbe Interactions and Immunity
- Respiratory Support and Mechanisms
- Infant Nutrition and Health
- Clinical Nutrition and Gastroenterology
- Bacterial Infections and Vaccines
- Animal testing and alternatives
- Asthma and respiratory diseases
- Chronic Lymphocytic Leukemia Research
- Caveolin-1 and cellular processes
- Head and Neck Surgical Oncology
- Amyotrophic Lateral Sclerosis Research
- Pneumonia and Respiratory Infections
- Cytomegalovirus and herpesvirus research
- Cancer-related molecular mechanisms research
- Meningioma and schwannoma management
- Immune cells in cancer
- Biomedical Text Mining and Ontologies
Duke University
2011-2024
Duke Medical Center
2011-2022
Duke University Hospital
2011-2022
North Carolina State University
2022
Cryptococcus neoformans is an opportunistic fungal pathogen that causes approximately 625,000 deaths per year from nervous system infections. Here, we leveraged a unique, genetically diverse population of C. sub-Saharan Africa, commonly isolated mopane trees, to determine how selective pressures in the environment coincidentally adapted for human virulence. Genome sequencing and phylogenetic analysis 387 isolates, representing global VNI African VNB lineages, highlighted deep, nonrecombining...
Cryptococcal meningitis (CM), caused primarily by Cryptococcus neoformans, is uniformly fatal if not treated. Treatment options are limited, especially in resource-poor geographical regions, and mortality rates remain high despite current therapies. Here we evaluated the vitro vivo activity of several compounds, including APX001A its prodrug, APX001, currently clinical development for treatment invasive fungal infections. These compounds target conserved Gwt1 enzyme that required...
ABSTRACT The pathogenic species of Cryptococcus are a major cause mortality owing to severe infections in immunocompromised as well immunocompetent individuals. Although antifungal treatment is usually effective, many patients relapse after treatment, and such cases, comparative analyses the genomes incident isolates may reveal evidence determinative, microevolutionary changes within host. Here, we analyzed serial cultured from cerebrospinal fluid specimens 18 South African with recurrent...
Cryptococcal meningitis is a lethal disease with few treatment options. The incidence remains high and intricately linked the HIV/AIDS epidemic. In many parts of world, fluconazole only agent that available for initial cryptococcal despite considerable evidence it associated suboptimal microbiological clinical outcomes. Fluconazole has fungistatic mode action: predominantly inhibits growth rather than causing fungal killing. Our work shows pattern activity caused by emergence resistance in...
Infection outcomes for cryptococcosis, most commonly caused by C. neoformans , are influenced host immune responses as well and pathogen genetics. Infecting yeast isolates genetically diverse; however, we lack a deep understanding of how this diversity impacts patient outcomes.
Cryptococcus neoformans is a major human central nervous system (CNS) fungal pathogen causing considerable morbidity and mortality. In this study, we provide the widest view to date of yeast transcriptome directly from subarachnoid space within cerebrospinal fluid (CSF). We captured transcriptomes C. various genotypes in 31 patients with cryptococcal meningoencephalitis as well several gattii infections. Using sequencing (RNA-seq) analyses, compared
Previous epidemiological and cost studies of fungal meningitis have largely focused on single pathogens, leading to a poor understanding the disease in general. We studied largest most diverse group patients date, over longest follow-up period, examine broad impact resource utilization within United States.The Truven Health Analytics MarketScan database was used identify with diagnosis States between 2000 2012. Patients primary cryptococcal, Coccidioides, Histoplasma, or Candida were...
Cryptococcal meningitis (CM) has emerged as the most common life-threatening fungal worldwide. Current management involves a sequential, longitudinal regimen of antifungals; despite significant improvement in survival compared with uniform mortality without treatment, this drug paradigm not led to consistent cure. Neurapheresis therapy, extracorporeal filtration yeasts from cerebrospinal fluid (CSF) infected hosts, is presented here novel, one-time therapy for CM. In vitro CSF through...
Cryptococcus neoformans is an opportunistic fungal pathogen that at its peak epidemic levels caused estimated million cases of cryptococcal meningitis per year worldwide. This species can grow in diverse environmental (trees, soil and bird excreta) host niches (intracellular microenvironments phagocytes free-living tissues). The genetic basic for adaptation to these different conditions not well characterized, as most experimental work has relied on a single reference strain C. . To identify...
Abstract TCR signaling plays a critical role in regulatory T cell (Treg) development. However, the mechanism for tissue-specific induction of Tregs periphery remains unclear. We observed that surfactant protein A (SP-A)–deficient mice have impaired expression Foxp3 and fewer CD25+Foxp3+ after ex vivo stimulation with LPS vivo. The addition exogenous SP-A completely reversed this phenotype. Although is known to inhibit proliferation under certain activation conditions, both IL-2 levels as...
ABSTRACT Invasive fungal infections are a significant public health concern, with mortality rates ranging from 20% to 85% despite current treatments. Therefore, we examined whether ketogenic diet could serve as successful treatment intervention in murine models of Cryptococcus neoformans and Candida albicans infection combination fluconazole—a low-cost, readily available antifungal therapy. The is high-fat, low-carbohydrate that promotes fatty acid oxidation an alternative glycolysis through...
Trehalose-6-phosphate synthase (TPS1) was identified as a virulence factor for Cryptococcus neoformans and promising therapeutic target. This study reveals previously unknown roles of TPS1 in evasion host defenses during pulmonary disseminated phases infection. In the infection model, TPS1-deleted ( tps1Δ ) Cryptococci are rapidly cleared by mouse lungs whereas TPS1-sufficent WT (H99) revertant : strains expand disseminate, causing 100% mortality. Rapid clearance mutant is T-cell independent...
Abstract Although many studies have shown that pulmonary surfactant protein (SP)-A functions in innate immunity, fewer addressed its role adaptive immunity and allergic hypersensitivity. We hypothesized SP-A modulates the phenotype prevalence of dendritic cells (DCs) CD4+ T to inhibit Th2-associated inflammatory indices associated with allergen-induced inflammation. In an OVA model hypersensitivity, SP-A−/− mice had greater eosinophilia, cytokine levels, IgE levels compared wild-type...
The human pathogen Cryptococcus neoformans is the leading cause of fungal meningitis in primarily immunocompromised populations. Understanding how this environmental organism adapts to host deadly infection will guide our development novel disease control strategies.
Cryptococcal meningitis (CM) is a fungal disease with significant global morbidity and mortality. The gepix Gwt1 inhibitors are new class of antifungal drugs.
Abstract Pulmonary surfactant lipoproteins lower the surface tension at alveolar–airway interface of lung and participate in host defense. Previous studies reported that protein A (SP-A) inhibits lymphocyte proliferation. We hypothesized SP-A–mediated modulation T cell activation depends upon strength, duration, type activating signals. Modulation signal strength imparted by different agents ex vivo mouse models vitro with human cells shows a strong correlation between (SoS) functional...
Cryptococcus spp., important fungal pathogens, are the leading cause of fungus-related mortality in human immunodeficiency virus-infected patients, and new therapeutic options desperately needed. Isavuconazonium sulfate, a newer triazole antifungal agent, was studied to characterize exposure-response relationship rabbit model cryptococcal meningoencephalitis. Rabbits treated with isavuconazonium sulfate were compared those fluconazole untreated controls.
Patients receiving the Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib have an increased likelihood of fungal infections. The objectives this study were to determine if Cryptococcus neoformans infection severity was isolate dependent with BTK inhibition and whether blocking impacted in a mouse model.
Abstract We previously observed a substantial burden of cryptococcal meningitis in Vietnam atypically arising individuals who are uninfected with human immunodeficiency virus (HIV). This disease was associated single genotype Cryptococcus neoformans (sequence type [ST]5), which significantly less common HIV-infected individuals. Aiming to compare the phenotypic characteristics ST5 and non-ST5 C. neoformans, we selected 30 representative Vietnamese isolates compared their vitro pathogenic...
Surfactant protein A (SP-A) mediates innate immune cell responses to LPS, a wall component of gram-negative bacteria that is found ubiquitously in the environment and associated with adverse health effects. Inhaled LPS induces lung inflammation increases airway responsiveness (AR). However, role SP-A mediating LPS-induced AR not well-defined. Nitric oxide (NO) described as potent bronchodilator, previous studies showed modulates production NO. Hence, we tested hypothesis increased AR,...
Graft-versus-host disease (GVHD) is a severe and frequent complication of allogeneic bone marrow transplantation (BMT) that involves the gastrointestinal (GI) tract lungs. The pathobiology GVHD complex immune cell recognition host Ags as foreign. We hypothesize central role for collectin surfactant protein A (SP-A) in regulating development after BMT. C57BL/6 (H2b; WT) SP-A-deficient mice on background SP-A(-/-)) underwent or syngeneic BMT with cells from either C3HeB/FeJ (H2k; recipient...
Leptomeningeal metastases (LM), late-stage cancer when malignant cells migrate to the subarachnoid space (SAS), have an extremely poor prognosis. Current treatment regimens fall short in effectively reducing SAS tumor burden. Neurapheresis therapy is a novel approach employing filtration and enhanced circulation of cerebrospinal fluid (CSF). Here, we examine vitro use neurapheresis as novel, adjunctive option for LM by filtering augmenting distribution drugs that may potential enhance...
APX001 is a first-in-class intravenous and orally available broad spectrum antifungal inhibitor of Gwt1, protein involved in glycosylphosphatidylinositol anchor biosynthesis. This study evaluated efficacy APX001, alone combination with fluconazole (FCN), mouse model cryptococcal meningitis. Mice (10/group) infected via tail vein Cryptococcus neoformans received FCN, both, or neither, for 7 days. was given as 390mg/kg thrice daily. FCN intraperitoneally 80mg/kg/day. Brain lung were cultured...
Thymectomy in neonatal rodents is an established and reliable procedure for immunological studies. However, adult rats, complications of hemorrhage pneumothorax from pleural disruption can result a significant mortality rate. This protocol simple method rat thymectomy that utilizes mini-sternotomy endotracheal intubation. Intubation accomplished with non-invasive easily reproducible allows positive pressure ventilation to prevent controlled airway sufficient time careful thymus dissection...
Thymectomy in neonatal rodents is an established and reliable procedure for immunological studies. However, adult rats, complications of hemorrhage pneumothorax from pleural disruption can result a significant mortality rate. This protocol simple method rat thymectomy that utilizes mini-sternotomy endotracheal intubation. Intubation accomplished with non-invasive easily reproducible allows positive pressure ventilation to prevent controlled airway sufficient time careful thymus dissection...