A5081848912- Antifungal resistance and susceptibility
- Fungal Infections and Studies
- Lipid Membrane Structure and Behavior
- Vector-borne infectious diseases
- Mycotoxins in Agriculture and Food
- HIV/AIDS drug development and treatment
- Viral Infections and Vectors
- Immune Cell Function and Interaction
- Cancer therapeutics and mechanisms
- Sphingolipid Metabolism and Signaling
- Fungal Biology and Applications
- Invertebrate Immune Response Mechanisms
- Viral Infections and Outbreaks Research
- Erythrocyte Function and Pathophysiology
- Mosquito-borne diseases and control
- Malaria Research and Control
- HIV Research and Treatment
- Antimicrobial Peptides and Activities
- Porphyrin and Phthalocyanine Chemistry
- Genomics and Rare Diseases
- Synthesis and Characterization of Heterocyclic Compounds
- Complement system in diseases
- Vitamin C and Antioxidants Research
- Bacterial biofilms and quorum sensing
- Hemoglobin structure and function
National Institute of Allergy and Infectious Diseases
2007-2023
National Institutes of Health
2007-2023
Office of Extramural Research
2020
ITRI International
2009
Georgetown University
1990
Gliotoxin is an immunosuppressive mycotoxin long suspected to be a potential virulence factor of Aspergillus fumigatus. Recent studies using mutants lacking gliotoxin production, however, suggested that the not important for pathogenesis A. fumigatus in neutropenic mice resulting from treatment with cyclophosphomide and hydrocortisone. In this study, we report on pathobiological role two different mouse strains, 129/Sv BALB/c, were immunosuppressed by hydrocortisone alone avoid neutropenia....
Staphylococcus aureus is a prominent human pathogen and leading cause of bacterial infection in hospitals the community. Community-associated methicillin-resistant S. (CA-MRSA) strains such as USA300 are highly virulent and, unlike hospital strains, often disease otherwise healthy individuals. The enhanced virulence CA-MRSA based part on increased ability to produce high levels secreted molecules that facilitate evasion innate immune response. Although progress has been made, factors...
Abstract The alternative sigma factor RpoS plays a central role in the critical host-adaptive response of Lyme disease spirochete, Borrelia burgdorferi . We previously identified bbd18 as negative regulator but could not inactivate wild-type spirochetes. In current study we employed an inducible gene to demonstrate essential nature BBD18 for viability spirochetes vitro and at unique point vivo. Transcriptomic analyses BBD18-depleted cells demonstrated global induction RpoS-dependent genes...
Summary Cryptococcus neoformans is a pathogenic yeast that causes life‐threatening meningoencephalitis and grows well on mycological media regardless of inoculum size. Interestingly, deletion the global repressor TUP1 in C. uncovered density‐dependent growth phenotype reminiscent quorum‐sensing phenomenon. An size lower than 10 3 cells tup1 Δ strain failed to form colonies agar while inocula 5 −10 6 per plate formed lawn. This phenotype, expressed as inability grow at low cell densities, was...
A recent report on several cases of invasive aspergillosis caused by Neosartorya udagawae suggested distinctive patterns disease progression between N. and Aspergillus fumigatus. This prompted us to characterize in comparison A. Our findings showed that both species exist two mating types at similar ratios produce gliotoxin. However, the thermotolerance differs: while fumigatus is able grow 55 degrees C but not 10 C, fails >42 C. Furthermore, compared fumigatus, conidia require longer...
The function of the antigen-5/CAP family proteins found in salivary gland bloodsucking animals has remained elusive for decades. Antigen-5 members from hematophagous insects Dipetalogaster maxima (DMAV) and Triatoma infestans (TIAV) were expressed discovered to attenuate platelet aggregation, ATP secretion, thromboxane A2 generation by low doses collagen (<1 μg/ml) but no other agonists. DMAV did not interact with collagen, glycoprotein VI, or integrin α2β1. This inhibitory profile resembles...
ABSTRACT The most common cause of invasive aspergillosis (IA) in patients with chronic granulomatous disease (CGD) is Aspergillus fumigatus followed by A. nidulans ; other aspergilli rarely the disease. Here we review two clinical cases fatal IA CGD and describe a new etiologic agent refractory to antifungal therapy. Unlike typical caused , species was spread from lung multiple adjacent organs. Mycological characteristics phylogenetic relationship based on sequence analysis Mcm7 RPB2 Tsr1...
Abstract Cholesterol, a necessary component of animal cell membranes, is also needed by the lethal human malaria parasite Plasmodium falciparum . Because P. lacks cholesterol synthesis pathway and patients have low blood cholesterol, we speculated that it scavenges from them in some way. We used time-lapse holotomographic microscopy to observe transport live parasites structurally investigate erythrocyte both during after invasion erythrocytes. After initially acquired free or inner...
Monoclonal antibody 2909 belongs to a class of potently neutralizing antibodies that recognize quaternary epitopes on HIV-1. Some members this class, such as 2909, are strain specific, while others, PG16, broadly neutralizing; all, however, region the gp120 envelope glycoprotein includes two loops (V2 and V3) forms appropriately only in oligomeric HIV-1 spike (gp120(3)/gp41(3)). Here we present crystal structure report structure-function analysis with chimeras composed other class. The was...
Virulent <i>Francisella tularensis</i> subsp. <i>tularensis</i> (Ftt) is a dynamic, intracellular, bacterial pathogen. Its ability to evade and rapidly suppress host inflammatory responses considered key element for its profound virulence. We previously established that Ftt lipids play role in inhibiting inflammation, but we did not determine the lipid species mediating this process. Here, show unique, abundant, phosphatidylethanolamine (PE), present...
Inhibition of nitric oxide (NO) signaling may contribute to pathological activation the vascular endothelium during severe malaria infection. Dimethylarginine dimethylaminohydrolase (DDAH) regulates endothelial NO synthesis by maintaining homeostasis between asymmetric dimethylarginine (ADMA), an endogenous synthase (NOS) inhibitor, and arginine, NOS substrate. We carried out a community-based case-control study Gambian children determine whether ADMA arginine is disrupted or uncomplicated...
Hemoglobin C differs from normal hemoglobin A by a glutamate-to-lysine substitution at position 6 of beta globin and is oxidatively unstable. Compared to homozygous AA erythrocytes, CC erythrocytes contain higher levels membrane-associated hemichromes more extensively clustered band 3 proteins. These findings suggest that have different membrane matrix than erythrocytes.We found differ in their lipid composition, subset expresses increased externalized phosphatidylserine. Detergent analyses...
Delayed diagnosis in invasive aspergillosis (IA) contributes to its high mortality. Gliotoxin (GT) and bis-methyl-gliotoxin (bmGT) are secondary metabolites produced by Aspergillus during invasive, hyphal growth may prove diagnostically useful. Because IA pathophysiology GT's role virulence vary depending on the underlying host immune status, we hypothesized that GT bmGT production vivo differ three mouse models of mimic human disease. We defined temporal kinetics serum, bronchoalveolar...
Abstract Cellular lysates from PPD+ donors have been reported to transfer tuberculin reactivity naïve recipients, but not diphtheria reactivity, and vice versa. A historically controversial topic, the terms “transfer factor” “DLE” were used characterize reactivity-transferring properties of lysates. Intrigued by these phenomena, we found that cellular extract derived antigen-specific memory CD8+ T cells induces IL-6 antigen-matched APCs. This ultimately elicits IL-17 bystander cells. We...
Blood-feeding disease vectors mitigate the negative effects of hemostasis and inflammation through binding small-molecule agonists these processes by salivary proteins. In this study, a lipocalin protein family member (LTBP1) from saliva Rhodnius prolixus, vector pathogen Trypanosoma cruzi, is shown to sequester cysteinyl leukotrienes during feeding inhibit immediate inflammatory responses. Calorimetric experiments showed that LTBP1 binds C4 (LTC4), D4 (LTD4), E4 (LTE4) but not biogenic...
The salivary glands of the flea Xenopsylla cheopis, a vector plague bacterium, Yersinia pestis, express proteins and peptides thought to target hemostatic inflammatory systems its mammalian hosts. Past transcriptomic analyses gland tissue revealed presence two similar (XC-42 XC-43) having no extensive similarities any other deposited sequences. Here we show that these specifically inhibit coagulation plasma amidolytic activity α-thrombin. XC-43, smaller peptides, is fast, tight-binding...
Abstract N G , ‐dimethyl‐ l ‐arginine (asymmetric dimethylarginine, ADMA), ‐monomethyl‐ ( ‐NMMA) and ’ (symmetric SDMA) are released during hydrolysis of proteins containing methylated arginine residues. ADMA ‐NMMA inhibit nitric oxide synthase by competing with substrate. All three methylarginine derivatives also transport. To enable investigation methylarginines in diseases involving impaired synthesis, we developed a high‐performance liquid chromatography (HPLC) assay to simultaneously...
In arthropods, hemolymph carries immune cells and solubilizes transports nutrients, hormones, other molecules that are involved in diverse physiological processes including immunity, metabolism, reproduction. However, despite such importance, little is known about its composition. We applied mass spectrometry-based label-free quantification approaches to study the proteome of perfused from sugar-fed female male Aedes aegypti mosquitoes. A total 1403 proteins were identified, out which 447...
WR99210, a former antimalarial drug candidate now widely used for the selection of Plasmodium transfectants, selectively targets parasite’s dihydrofolate reductase thymidine synthase bifunctional enzyme (DHFR-TS) but not human DHFR, which is fused with TS. Accordingly, WR99210 and plasmids expressing dhfr gene have become valued tools genetic modification parasites in laboratory. Concerns over ineffectiveness from some sources encouraged us to investigate biological chemical differences...