A5075395368- Malaria Research and Control
- Bacteriophages and microbial interactions
- Drug Transport and Resistance Mechanisms
- HIV/AIDS drug development and treatment
- Mosquito-borne diseases and control
- Computational Drug Discovery Methods
- Trypanosoma species research and implications
- Virus-based gene therapy research
- Drug-Induced Hepatotoxicity and Protection
- Genomics and Phylogenetic Studies
- RNA and protein synthesis mechanisms
- Cancer therapeutics and mechanisms
- Cytomegalovirus and herpesvirus research
- HIV Research and Treatment
- Synthesis and Catalytic Reactions
- Synthesis and Characterization of Heterocyclic Compounds
- Microbial infections and disease research
- Evolution and Genetic Dynamics
- Biosensors and Analytical Detection
- Herpesvirus Infections and Treatments
- Antimicrobial Resistance in Staphylococcus
- Viral gastroenteritis research and epidemiology
- Phenothiazines and Benzothiazines Synthesis and Activities
- CRISPR and Genetic Engineering
- Enterobacteriaceae and Cronobacter Research
National Institute of Allergy and Infectious Diseases
2015-2023
National Institutes of Health
2015-2023
Virginia Commonwealth University
2010-2015
Old Dominion University
2005-2009
Munster Technological University
2007
Staphylococcal pathogenicity islands (SaPIs) carry superantigen and resistance genes are extremely widespread in Staphylococcus aureus other Gram-positive bacteria. SaPIs represent a major source of intrageneric horizontal gene transfer stealth conduit for intergeneric transfer; they phage satellites that exploit the life cycle their temperate helper phages with elegant precision to enable rapid replication promiscuous spread. also interfere reproduction, blocking plaque formation, sharply...
Summary Mutations in the Plasmodium falciparum chloroquine (CQ) resistance transporter (PfCRT) can result verapamil‐reversible CQ and altered susceptibility to other antimalarials. PfCRT contains 10 membrane‐spanning domains is found digestive vacuole (DV) membrane of intraerythrocytic parasites. The mechanism by which mediates unclear although it associated with decreased accumulation drug within DV. On permissive background P. 106/1 K76 parasite line, we used single‐step selection generate...
Significance The mitochondrial electron transport chain (ETC) of Plasmodium falciparum malaria parasites contains targets for antimalarial drug development including cytochrome B (PfCytB) and NADH dehydrogenase 2 (PfNDH2). Atovaquone (ATQ), a widely used drug, is hydroxynaphthoquinone inhibitor PfCytB; substituted quinolone compounds (CK-2-68 RYL-552) have also been developed as putative inhibitors PfNDH2. Unexpectedly, our experiments yielded mutations PfCytB, not PfNDH2, in selected with...
A series of novel 10-N-substituted acridones, bearing alkyl side chains with tertiary amine groups at the terminal position, were designed, synthesized, and evaluated for ability to enhance potency quinoline drugs against multidrug-resistant (MDR) Plasmodium falciparum malaria parasites. number acridone derivatives, bridged three or more carbon atoms apart between ring nitrogen nitrogen, demonstrated chloroquine (CQ)-chemosensitizing activity MDR strain P. (Dd2). Isobologram analysis...
Protein ubiquitination is an important posttranslational regulation mechanism that mediates Plasmodium development and modifies parasite responses to antimalarial drugs. Although mutations in several enzymes have been linked increased drug tolerance, the molecular mechanisms by which pathways mediate these remain largely unknown. Here, we investigate roles of a falciparum ring finger ubiquitin ligase (PfRFUL) We engineered transgenic having Pfrful gene tagged with HA-2A-NeoR-glmS sequence...
Among the various components of protozoan Plasmodium mitochondrial respiratory chain, only Complex III is a validated cellular target for antimalarial drugs. The compound CK-2-68 was developed to specifically alternate NADH dehydrogenase malaria parasite but true its activity has been controversial. Here, we report cryo-EM structure mammalian bound with and examine structure–function relationships inhibitor's selective action on Plasmodium. We show that binds quinol oxidation site III,...
Lumefantrine and mefloquine are used worldwide in artemisinin-based combination therapy (ACT) of malaria. Better understanding drug susceptibility resistance is needed can be obtained from studies genetic crosses. Drug response phenotypes a cross between Plasmodium falciparum lines 803 (Cambodia) GB4 (Ghana) were as half-maximal effective concentrations (EC50s) days to recovery (DTR) after 24 h exposure 500 nM lumefantrine. EC50s mefloquine, halofantrine, chloroquine, dihydroartemisinin also...
Enteric adenoviruses have been shown to be a substantial cause of pediatric gastroenteritis in various parts the world, and are considered second most common viral gastroenteritis, next rotavirus young children. Genetic characterization 95 adenovirus isolates obtained from patients with acute between 2002 2007 southern regions Ireland, were characterized by PCR analysis, restriction endonuclease (RE) analysis sequencing analysis. All found type 41 origin. seven hypervariable (HVRs) located...
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...
In the article by Cooper et al. (2007) an error appeared in Fig. 8.In TMD 4 of PfCRT, amino acids 168-177 were numbered incorrectly.
ABSTRACT WR99210, a former antimalarial drug candidate now widely used for the selection of Plasmodium transfectants, selectively targets parasite dihydrofolate reductase thymidine synthase bifunctional enzyme (DHFR-TS) but not human DHFR, which is fused with TS. Accordingly, WR99210 and plasmids expressing dhfr have become valued tools genetic modification parasites in laboratory. Concerns over ineffectiveness from some sources encouraged us to investigate biological chemical differences...