A5067549205- Malaria Research and Control
- Mosquito-borne diseases and control
- Computational Drug Discovery Methods
- Trypanosoma species research and implications
- Drug Transport and Resistance Mechanisms
- Hemoglobinopathies and Related Disorders
- Invertebrate Immune Response Mechanisms
- Aquaculture disease management and microbiota
- HIV/AIDS drug development and treatment
- Complement system in diseases
- Vector-borne infectious diseases
- Drug-Induced Hepatotoxicity and Protection
- Antibiotic Resistance in Bacteria
- HIV Research and Treatment
- Neonatal Health and Biochemistry
- Viral Infectious Diseases and Gene Expression in Insects
- Toxoplasma gondii Research Studies
- Lipid Membrane Structure and Behavior
- Research on Leishmaniasis Studies
- Parasitic Infections and Diagnostics
- Erythrocyte Function and Pathophysiology
- Plant Virus Research Studies
- Viral Infections and Vectors
- RNA and protein synthesis mechanisms
- Parasites and Host Interactions
National Institute of Allergy and Infectious Diseases
2016-2025
National Institutes of Health
2015-2024
Applied Genetic Technologies (United States)
2023
University of Georgia
2000-2023
Government of the United States of America
2023
Vector Oncology (United States)
2005-2021
Vector (United States)
2004-2019
University of Chicago
1978-2019
Rockefeller Archive Center
2019
American Society For Testing and Materials
2010
Chloroquine-resistant Plasmodium falciparum malaria is a major health problem, particularly in sub-Saharan Africa. Chloroquine resistance has been associated vitro with point mutations two genes, pfcrt and pfmdr 1, which encode the P. digestive-vacuole transmembrane proteins PfCRT Pgh1, respectively.To assess value of these as markers for clinical chloroquine resistance, we measured association between response to treatment patients uncomplicated Mali. The frequencies before after were...
Malaria parasites are haploid for most of their life cycle, with zygote formation and meiosis occurring during the mosquito phase development. The can be analyzed genetically by transmitting mixtures cloned through mosquitoes to permit cross-fertilization gametes occur. A cross was made between two clones Plasmodium falciparum differing in enzymes, drug sensitivity, antigens, chromosome patterns. Parasites showing recombination parent clone markers were detected at a high frequency. Novel...
"Pyrimethamine and Proguanil Resistance-Conferring Mutations in Plasmodium falciparum Dihydrofolate Reductase: Polymerase Chain Reaction Methods for Surveillance Africa" published on Jun 1995 by The American Society of Tropical Medicine Hygiene.
Analysis of a genetic cross Plasmodium falciparum and independent parasite isolates from Southeast Asia, Africa, South America indicates that resistance to pyrimethamine, an antifolate used in the treatment malaria, results point mutations gene encoding dihydrofolate reductase-thymidylate synthase (EC 1.5.1.3 EC 2.1.1.45, respectively). Parasites having mutation Thr-108/Ser-108 Asn-108 DHFR-TS are resistant drug. The occurs region analogous C alpha-helix bordering active site cavity...
Increasing resistance of Plasmodium falciparum malaria parasites to chloroquine and the dihydrofolate reductase (DHFR) inhibitors pyrimethamine cycloguanil have sparked renewed interest in antimalarial drugs WR99210 proguanil, precursor. To investigate suggestions that proguanil act against a target other than moiety P. bifunctional DHFR–thymidylate synthase enzyme, we transformed with variant form human DHFR selectable by methotrexate. Human was found fully negate antiparasitic effect...
Proguanil and pyrimethamine are antifolate drugs with distinct chemical structures that used commonly in the prophylaxis treatment of Plasmodium falciparum malaria. Clinical reports field studies have suggested some parasites refractory to proguanil can be treated pyrimethamine, vice versa. Analysis P. dihydrofolate reductase (DHFR) from different reveals structural basis for differential susceptibility these drugs. Parasites harboring a pair point mutations Ala-16 Val-16 Ser-108 Thr-108...
Plasmodium falciparum malaria parasites within human red blood cells (RBCs) have been successfully transfected to produce chloramphenicol acetyltransferase (CAT). Electroporation of parasitized RBCs was used introduce plasmids that CAT-encoding DNA flanked by 5' and 3' untranslated sequences the P. hsp86, hrp3, hrp2 genes. These flanking were required for expression as their excision abolished CAT activity in parasites. Transfection signals from native compared well with those a synthetic...
Plasmodium falciparum malaria parasites were transformed with plasmids containing P. or Toxoplasma gondii dihydrofolate reductase-thymidylate synthase (dhfr-ts) coding sequences that confer resistance to pyrimethamine. Under pyrimethamine pressure, obtained maintained the transfected as unrearranged episomes for several weeks. These parasite populations replaced after 2 3 months by had incorporated DNA into nuclear chromosomes. Depending upon particular construct used transformation,...
Since the 1970s, when Chinese researchers demonstrated artemisinins' antimalarial potency, artemisinin-based combination therapy has become key to malaria control. But reduced susceptibility of Plasmodium falciparum artemisinin is now being seen in some places.
The malaria parasite Plasmodium falciparum has a great capacity for evolutionary adaptation to evade host immunity and develop drug resistance. Current understanding of evolution is impeded by the fact that large fraction genome either highly repetitive or variable thus difficult analyze using short-read sequencing technologies. Here, we describe resource deep data on parents progeny from genetic crosses, which enabled us perform first genome-wide, integrated analysis SNP, indel complex...
ABSTRACT Plasmodium vivax causes heavy burdens of disease across malarious regions worldwide. Mature P. asexual and transmissive gametocyte stages occur in the blood circulation, it is often assumed that accumulation/sequestration tissues not an important phase their development. Here, we present a systematic study stage distributions infected nonhuman primate (NHP) malaria models as well from human infections. In comparative analysis transcriptomes falciparum blood-stage parasites, found...
Plasmodium falciparum-infected erythrocytes (IRBCs) synthesize several histidine-rich proteins (HRPs) that accumulate high levels of [3H]histidine but very low amino acids such as [3H]isoleucine or [35S]methionine. We prepared a monoclonal antibody which reacts specifically with one these HRPs (Pf HRP II) and studied the location synthesis this protein during parasite's intracellular growth. With knob-positive Malayan Camp strain P. falciparum, identified multiplet bands major species at Mr...
The resurgence of malaria in recent decades has been accompanied by the worldwide spread resistance to chloroquine, a drug once uncontested as first-line antimalarial agent because its efficacy and low toxicity. Chloroquine-resistant strains Plasmodium falciparum counter expelling it rapidly via an unknown mechanism. In absence explicit biochemical knowledge this efflux mechanism, reverse genetics provides powerful approach molecular basis chloroquine resistance. Here we report genetic...
Chloroquine (CQ) resistance (CQR) in Plasmodium falciparum originated from at least six foci South America, Asia, and Oceania. Malaria parasites these locations exhibit contrasting phenotypes that are distinguished by point mutations microsatellite polymorphisms near the CQR transporter gene, pfcrt, multidrug pfmdr1. Amodiaquine (AQ), a 4-aminoquinoline related to CQ, is recommended often used successfully against CQ-resistant P. Africa, but it largely ineffective across large regions of...
Glucose-6-phosphate dehydrogenase (G6PD) is important in the control of oxidant stress erythrocytes, host cells for Plasmodium falciparum. Mutations this enzyme produce X-linked deficiency states associated with protection against malaria, notably Africa where A- form G6PD widespread. Some reports have proposed that heterozygous females mosaic populations normal and deficient erythrocytes (due to random X chromosome inactivation) malaria resistance similar or greater than hemizygous males...