Kristin D. Lane

Structure of complex III with bound antimalarial agent CK-2-68 provides insights into selective inhibition of Plasmodium cytochrome bc1 complexes

Lothar Esser, Fei Zhou, Allison Zeher, Weimin Wu et autres

Among the various components of the 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 target the alternate NADH dehydrogenase of the malaria parasite respiratory chain, but the …

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A Plasmodium falciparum RING Finger E3 Ubiquitin Ligase Modifies the Roles of PfMDR1 and PfCRT in Parasite Drug Responses

Brajesh K. Singh, Cui Zhang, Jian Wu, Yu‐Chih Peng et autres

expression using glucosamine (GlcN). A Western blot analysis of the proteins from GlcN-treated pSLI-HA-NeoR-glmS-tagged (PfRFULg) parasites, relative to their wild-type (Dd2) controls, showed changes in the ubiquitination of numerous proteins. PfRFUL KD rendered the parasites more sensitive to multiple antimalarial drugs, including …

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Evidence for linkage of pfmdr1, pfcrt, and pfk13 polymorphisms to lumefantrine and mefloquine susceptibilities in a Plasmodium falciparum cross

Sean T. Windle, Kristin D. Lane, Nahla B. Gadalla, Anna Liu et autres

Lumefantrine and mefloquine are used worldwide in artemisinin-based combination therapy (ACT) of malaria. Better understanding of drug susceptibility and resistance is needed and can be obtained from studies of genetic crosses. Drug response phenotypes of a cross between Plasmodium falciparum lines 803 …

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Regioisomerization of Antimalarial Drug WR99210 Explains the Inactivity of a Commercial Stock

Thomas Parks Remcho, Sravanthi D. Guggilapu, Phillip Cruz, Glenn A. Nardone et autres

WR99210, a former antimalarial drug candidate now widely used for the selection of Plasmodium transfectants, selectively targets the parasite’s dihydrofolate reductase thymidine synthase bifunctional enzyme (DHFR-TS) but not human DHFR, which is not fused with TS. Accordingly, WR99210 and plasmids expressing the …

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Isomerization of antimalarial drug WR99210 explains its inactivity in a commercial stock

Thomas Parks Remcho, Sravanthi D. Guggilapu, Phillip Cruz, Glenn A. Nardone et autres

ABSTRACT WR99210, a former antimalarial drug candidate now widely used for the selection of Plasmodium transfectants, selectively targets the parasite dihydrofolate reductase thymidine synthase bifunctional enzyme (DHFR-TS) but not human DHFR, which is not fused with TS. Accordingly, WR99210 and plasmids expressing …

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Plasmodium Genomics and Genetics: New Insights into Malaria Pathogenesis, Drug Resistance, Epidemiology, and Evolution

Xin‐zhuan Su, Kristin D. Lane, Xia Lu, Juliana M. Sá et autres

Protozoan Plasmodium parasites are the causative agents of malaria, a deadly disease that continues to afflict hundreds of millions of people every year. Infections with malaria parasites can be asymptomatic, with mild or severe symptoms, or fatal, depending on many factors such …

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Selection of Plasmodium falciparum cytochrome B mutants by putative PfNDH2 inhibitors

Kristin D. Lane, Jianbing Mu, Jinghua Lu, Sean T. Windle et autres

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 antimalarial drug, is a hydroxynaphthoquinone inhibitor of PfCytB; substituted quinolone …

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Fusion of field studies and the laboratory solves a puzzle in antimalarial resistance

Carol Hopkins Sibley, Kristin D. Lane

Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans the biological, physical, and social sciences.

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Corrigendum to sequence determinants for DNA packaging specificity in the S. aureus Pathogenicity Island SaPI1 [Plasmid 71 (2014) 8–15]

Joana C. Bento, Kristin D. Lane, Erik K. Read, Nuno Cerca et autres

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Sequence determinants for DNA packaging specificity in the S. aureus pathogenicity island SaPI1

Joana C. Bento, Kristin D. Lane, Erik K. Read, Nuno Cerca et autres

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Transcriptional crosstalk between helper bacteriophages and Staphylococcal aureus pathogenicity islands

Kristin D. Lane

Acquisition of a superantigen pathogenicity island (SaPI) significantly increases virulence in Staphylococcus aureus. Horizontal transfer of SaPIs occurs at high frequency and depends upon a helper bacteriophage, either through direct infection or SOS-mediated induction of a lysogen. SaPIs hijack the packaging machinery …

Staphylococcal pathogenicity island interference with helper phage reproduction is a paradigm of molecular parasitism

Geeta Ram, John Yu-Shen Chen, Krishan Kumar, Hope F. Ross et autres

Staphylococcal pathogenicity islands (SaPIs) carry superantigen and resistance genes and are extremely widespread in Staphylococcus aureus and in other Gram-positive bacteria. SaPIs represent a major source of intrageneric horizontal gene transfer and a stealth conduit for intergeneric gene transfer; they are phage …

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