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Whole genome sequencing identifies novel mutations in malaria parasites resista...

Cassiano, Gustavo Capatti; Martinelli, Axel; Mottin, Melina; Neves, Bruno Junior; Andrade, Carolina Horta; Ferreira, Pedro Eduardo; Cravo, Pedro

Funding Information: The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. The authors would like to acknowledge i. the Portuguese “Fundação para a Ciência e Tecnologia (FCT)” for funds to GHTM – UID/Multi/04413/2020, LA-REAL-LA/P/0117/2020 and for funds to Pedro Ferreira`s project ref. PTDC/SAU-PAR/2766/2021 and ii. the Brazilian funding age...


Artemisinin resistance in rodent malaria - Mutation in the AP2 adaptor μ-chain ...

Henriques, Gisela; Martinelli, Axel; Rodrigues, Louise; Modrzynska, Katarzyna; Fawcett, Richard; Houston, Douglas R.; Borges, Sofia T.

Background: The control of malaria, caused by Plasmodium falciparum, is hampered by the relentless evolution of drug resistance. Because artemisinin derivatives are now used in the most effective anti-malarial therapy, resistance to artemisinin would be catastrophic. Indeed, studies suggest that artemisinin resistance has already appeared in natural infections. Understanding the mechanisms of resistance would h...


Quantitative genome re-sequencing defines multiple mutations conferring chloroq...

Kinga Modrzynska, Katarzyna; Creasey, Alison; Loewe, Laurence; Cezard, Timothee; Trindade Borges, Sofia; Martinelli, Axel; Rodrigues, Louise

Background: Drug resistance in the malaria parasite Plasmodium falciparum severely compromises the treatment and control of malaria. A knowledge of the critical mutations conferring resistance to particular drugs is important in understanding modes of drug action and mechanisms of resistances. They are required to design better therapies and limit drug resistance.A mutation in the gene (pfcrt) encoding a membra...


Experimental evolution of resistance to artemisinin combination therapy results...

Rodrigues, Louise A; Henriques, Gisela; Borges, Sofia T; Hunt, Paul; Sanchez, Cecília P; Martinelli, Axel; Cravo, Pedro

BACKGROUND: Lacking suitable alternatives, the control of malaria increasingly depends upon Artemisinin Combination Treatments (ACT): resistance to these drugs would therefore be disastrous. For ACTs, the biology of resistance to the individual components has been investigated, but experimentally induced resistance to component drugs in combination has not been generated. METHODOLOGY/PRINCIPAL FINDINGS: We have...


Geographic structuring of the Plasmodium falciparum sarco(endo)plasmic reticulu...

Jambou, Ronan; Martinelli, Axel; Pinto, João; Gribaldo, Simonetta; Legrand, Eric; Niang, Makhtar; Kim, Nimol; Pharath, Lim; Volnay, Béatrice

Artemisinin, a thapsigargin-like sesquiterpene has been shown to inhibit the Plasmodium falciparum sarco/endoplasmic reticulum calcium-ATPase PfSERCA. To collect baseline pfserca sequence information before field deployment of Artemisinin-based Combination therapies that may select mutant parasites, we conducted a sequence analysis of 100 isolates from multiple sites in Africa, Asia and South America. Coding se...


Experimental evolution, genetic analysis and genome re-sequencing reveal the mu...

Hunt, Paul; Martinelli, Axel; Modrzynska, Katarzyna; Borges, Sofia; Creasey, Alison; Rodrigues, Louise; Beraldi, Dario; Loewe, Laurence

Background: Classical and quantitative linkage analyses of genetic crosses have traditionally been used to map genes of interest, such as those conferring chloroquine or quinine resistance in malaria parasites. Next-generation sequencing technologies now present the possibility of determining genome-wide genetic variation at single base-pair resolution. Here, we combine in vivo experimental evolution, a rapid g...


An AFLP-based genetic linkage map of Plasmodium chabaudi chabaudi

Martinelli, Axel; Hunt, Paul; Fawcett, Richard; Cravo, Pedro V L; Walliker, David; Carter, Richard

BACKGROUND: Plasmodium chabaudi chabaudi can be considered as a rodent model of human malaria parasites in the genetic analysis of important characters such as drug resistance and immunity. Despite the availability of some genome sequence data, an extensive genetic linkage map is needed for mapping the genes involved in certain traits. METHODS: The inheritance of 672 Amplified Fragment Length Polymorphism (AFLP...


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