In vivo hypermutation and continuous evolution

RS Molina, G Rix, AA Mengiste, B Álvarez… - Nature Reviews …, 2022 - nature.com
Directed evolution has revolutionized biomolecular engineering by applying cycles of
mutation, amplification and selection to genes of interest (GOIs). However, classical directed …

Bacterial resistance to antibiotics: modified target sites

PA Lambert - Advanced drug delivery reviews, 2005 - Elsevier
Alteration in the target sites of antibiotics is a common mechanism of resistance. Examples
of clinical strains showing resistance can be found for every class of antibiotic, regardless of …

Scalable, continuous evolution of genes at mutation rates above genomic error thresholds

A Ravikumar, GA Arzumanyan, MKA Obadi… - Cell, 2018 - cell.com
Directed evolution is a powerful approach for engineering biomolecules and understanding
adaptation. However, experimental strategies for directed evolution are notoriously labor …

Oxidative stress and protein damage responses mediate artemisinin resistance in malaria parasites

F Rocamora, L Zhu, KY Liong, A Dondorp… - PLoS …, 2018 - journals.plos.org
Due to their remarkable parasitocidal activity, artemisinins represent the key components of
first-line therapies against Plasmodium falciparum malaria. However, the decline in efficacy …

Transformation with human dihydrofolate reductase renders malaria parasites insensitive to WR99210 but does not affect the intrinsic activity of proguanil

DA Fidock, TE Wellems - Proceedings of the National …, 1997 - National Acad Sciences
Increasing resistance of Plasmodium falciparum malaria parasites to chloroquine and the
dihydrofolate reductase (DHFR) inhibitors pyrimethamine and cycloguanil have sparked …

Malarial dihydrofolate reductase as a paradigm for drug development against a resistance-compromised target

Y Yuthavong, B Tarnchompoo… - Proceedings of the …, 2012 - National Acad Sciences
Malarial dihydrofolate reductase (DHFR) is the target of antifolate antimalarial drugs such as
pyrimethamine and cycloguanil, the clinical efficacy of which have been compromised by …

Insights into antifolate resistance from malarial DHFR-TS structures

J Yuvaniyama, P Chitnumsub… - Nature Structural & …, 2003 - nature.com
Plasmodium falciparum dihydrofolate reductase–thymidylate synthase (PfDHFR-TS) is an
important target of antimalarial drugs. The efficacy of this class of DHFR-inhibitor drugs is …

Pyrimethamine–sulfadoxine resistance in Plasmodium falciparum: what next?

CH Sibley, JE Hyde, PFG Sims, CV Plowe… - Trends in …, 2001 - cell.com
Chemotherapy remains the only practicable tool to control falciparum malaria in sub-
Saharan Africa, where> 90% of the world's burden of malaria mortality and morbidity occurs …

Mutations in Plasmodium falciparum Dihydrofolate Reductase and Dihydropteroate Synthase and Epidemiologic Patterns of Pyrimethamine-Sulfadoxine Use and …

CV Plowe, JF Cortese, A Djimde… - Journal of Infectious …, 1997 - academic.oup.com
To assess the relationship between mutations in Plasmodium falciparum dihydrofolate
reductase (DHFR) and dihydropteroate synthase (DHPS) and clinical pyrimethamine …

Malaria chemotherapeutics part I: History of antimalarial drug development, currently used therapeutics, and drugs in clinical development

M Schlitzer - ChemMedChem: Chemistry Enabling Drug …, 2007 - Wiley Online Library
Since ancient times, humankind has had to struggle against the persistent onslaught of
pathogenic microorganisms. Nowadays, malaria is still the most important infectious disease …