A5034492000- Fungal Infections and Studies
- Malaria Research and Control
- Antifungal resistance and susceptibility
- Plant biochemistry and biosynthesis
- Microbial Natural Products and Biosynthesis
- Trypanosoma species research and implications
- Biochemical and Molecular Research
- Genomics and Phylogenetic Studies
- Nail Diseases and Treatments
- Aquaculture disease management and microbiota
- Erythrocyte Function and Pathophysiology
- Toxin Mechanisms and Immunotoxins
- Heat shock proteins research
- Toxoplasma gondii Research Studies
- Herpesvirus Infections and Treatments
- Immune Cell Function and Interaction
- Enzyme Structure and Function
- Neonatal Health and Biochemistry
- Hemoglobinopathies and Related Disorders
- Research on Leishmaniasis Studies
- Plant-Microbe Interactions and Immunity
- Microbial Inactivation Methods
- Microbial Metabolism and Applications
- Parasitic Infections and Diagnostics
- Proteins in Food Systems
University of Iowa
2020-2024
Washington University in St. Louis
2014-2022
University of Nebraska at Omaha
2014
Bioengineering Center
2014
National Center for Genetic Engineering and Biotechnology
2014
John Wiley & Sons (United States)
2014
Parasites make it hard to fight viruses Microbial co-infections challenge the immune system—different pathogens often require different flavors of responses for their elimination or containment (see Perspective by Maizels and Gause). Two teams studied what happens when parasitic worms infect mice at same time. Reese et al. found that parasite co-infection woke up a dormant virus. Osborne already infected with were worse fighting off viruses. In both cases, skewed response so cells molecules...
Abstract Cryptococcus spp. are environmental fungi that first must adapt to the host environment before they can cause life-threatening meningitis in immunocompromised patients. Host CO 2 concentrations 100-fold higher than external and strains unable grow at not pathogenic. Using a genetic screening transcriptional profiling approach, we report TOR pathway is critical for C. neoformans adaptation partly through Ypk1-dependent remodeling of phosphatidylserine asymmetry plasma membrane. We...
During its complex life cycle, the malaria parasite survives dramatic environmental stresses, including large temperature shifts. Protein prenylation is required during asexual replication of Plasmodium falciparum , and canonical heat shock protein 40 (HSP40; PF3D7_1437900) posttranslationally modified with a 15-carbon farnesyl isoprenyl group.
Unique and essential aspects of parasite metabolism are excellent targets for development new antimalarials. An improved understanding drug resistance mechanisms is urgently needed. The antibiotic fosmidomycin the synthesis isoprenoid compounds from glucose a candidate antimalarial development. Our report identifies novel mechanism further describes family metabolic regulators in parasite. Using forward genetic approach, we also uncovered mutations that suppress glycolytic enzyme PFK9. Thus,...
Glycolysis controls cellular energy, redox balance, and biosynthesis. Antiglycolytic therapies are under investigation for treatment of obesity, cancer, aging, autoimmunity, microbial diseases. Interrupting glycolysis is highly valued as a therapeutic strategy, because glycolytic disruption generally tolerated in mammals. Unfortunately, anemia known dose-limiting side effect these inhibitors presents major caveat to development antiglycolytic therapies. We developed specific enolase –...
Abstract The opportunistic human fungal pathogen Cryptococcus neoformans has tremendous impact on global health, causing 181,000 deaths annually. Current treatment options are limited, and the frequent development of drug resistance exacerbates challenge managing invasive cryptococcal infections. In diverse pathogens, essential molecular chaperone Hsp90 governs survival, resistance, virulence. Therefore, targeting this emerged as a promising approach to combat However, role in supporting C....
Glucose transport in humans is a vital process which tightly regulated by the endocrine system. Specifically, insulin hormone triggers cascade of intracellular signals target cells mediating uptake glucose. Insulin signaling cellular relocalization glucose transporter protein GLUT4 to cell surface, primarily responsible for import. Pathology associated with disruption this pathway can lead metabolic disorders, such as type II diabetes mellitus, characterized failure appropriately from blood....
Coagulase-positive staphylococci, which frequently colonize the mucosal surfaces of animals, also cause a spectrum opportunistic infections including skin and soft tissue infections, urinary tract pneumonia, bacteremia. However, recent advances in bacterial identification have revealed that these common veterinary pathogens are fact zoonoses serious human patients. The global spread multidrug-resistant zoonotic particular emergence methicillin-resistant organisms, is now threat to both...
Cryptococcal meningoencephalitis remains a global health threat with limited treatment options. Currently, the most effective regimens are based on combination therapy of flucytosine either amphotericin B or fluconazole. Slow but steady progress is being made toward universal access to flucytosine-based therapies. The broadening therapies will be accompanied by need for microbiological methods that reliably determine strain susceptibility. This especially true considering susceptibility can...
The northern leopard frog Rana (Lithobates) pipiens is an important animal model, being used extensively in cancer, neurology, physiology, and biomechanical studies. R. a native North American whose range extends from Canada to southwest United States, but over the past few decades its populations have declined significantly now considered uncommon large portions of States Canada. To aid study conservation pipiens, this paper describes first transcriptome. transcriptome was annotated using...
Plasmodium parasites rely heavily on glycolysis for ATP production and precursors essential anabolic pathways, such as the methylerythritol phosphate (MEP) pathway. Here, we show that mutations in falciparum glycolytic enzyme, phosphofructokinase (PfPFK9), are associated with vitro resistance to a primary sulfonamide glycoside (PS-3). Flux through upper pathway was significantly reduced PS-3-resistant parasites, which levels but increased flux into pentose PS-3 may directly or indirectly...
Acetyl CoA synthetases (ACSs) are
The adaptation of environmental fungal pathogens to the mammalian host is critical pathogenesis. Of these adaptations, remodeling carbon metabolism particularly important.
Introduction An attractive, yet unrealized, goal in cancer therapy is repurposing psychiatric drugs that can readily penetrate the blood-brain barrier for treatment of primary brain tumors and metastases. Phenothiazines (PTZs) have demonstrated anti-cancer properties through a variety mechanisms. However, it remains unclear whether these effects are entirely separate from their activity as dopamine serotonin receptor (DR/5-HTR) antagonists. Methods In this study, we evaluated efficacy novel...
There is an urgent need for new antifungals to treat cryptococcal meningoencephalitis, a leading cause of mortality in people living with HIV/AIDS. An important aspect antifungal drug development the validation targets determine whether they are required survival organism animal models disease. In Cryptococcus neoformans, copper-regulated promoter (pCTR4-2) has been used previously modulate gene expression
Efforts to control the global malaria health crisis are undermined by antimalarial resistance. Identifying mechanisms of resistance will uncover underlying biology Plasmodium falciparum parasites that allow evasion our most promising therapeutics and may reveal new drug targets. We utilized fosmidomycin (FSM) as a chemical inhibitor plastidial isoprenoid biosynthesis through methylerythritol phosphate (MEP) pathway. have thus identified an unusual metabolic regulation scheme in parasite...
Cryptococcus neoformans is an environmental yeast and opportunistic human pathogen. The ability to cause disease depends on the adapt host. Previous studies implicated
is a ubiquitous environmental fungus and frequent colonizer of human lungs. Colonization can lead to diverse outcomes, from clearance long-term colonization life-threatening meningoencephalitis. Regardless the outcome, process starts with an encounter phagocytes. Using zebrafish model this infection, we have noted that cryptococcal cells first spend time inside macrophages before they become capable pathogenic replication dissemination. What "licensing" takes place during initial encounter,...
Abstract During its complex life cycle, the malaria parasite survives dramatic changes in environmental temperature. Protein prenylation is required during asexual replication of Plasmodium falciparum , and heat shock protein 40 (HSP40; PF3D7_1437900) post-translationally modified with a 15-carbon farnesyl isoprenyl group. In other organisms, farnesylation Hsp40 orthologs controls localization function, including temperature stress survival. this work, we find that plastidial isopentenyl...
ABSTRACT In the malaria parasite Plasmodium falciparum , synthesis of isoprenoids from glycolytic intermediates is essential for survival. The antimalarial fosmidomycin (FSM) inhibits isoprenoid synthesis. P. we identify a loss-of-function mutation in HAD2 (PF3D7_1226300) as necessary FSM resistance. Enzymatic characterization reveals that HAD2, member haloacid dehalogenase-like hydrolase (HAD) superfamily, phosphatase. Harnessing growth defect resistant parasites, select suppression...