Malaria Parasites Can Develop Stable Resistance to Artemisinin but Lack Mutations in Candidate Genes atp6 (Encoding the Sarcoplasmic and Endoplasmic Reticulum Ca2+ ATPase), tctp, mdr1, and cg10

ABSTRACT Resistance of Plasmodium falciparum to drugs such as chloroquine and sulfadoxine-pyrimethamine is a major problem in malaria control. Artemisinin (ART) derivatives, particularly in combination with other drugs, are thus increasingly used to treat malaria, reducing the probability that parasites resistant to the components will emerge. Although stable resistance to artemisinin has yet to be reported from laboratory or field studies, its emergence would be disastrous because of the lack of alternative treatments. Here, we report for the first time, to our knowledge, genetically stable and transmissible ART and artesunate (ATN)-resistant malaria parasites. Each of two lines of the rodent malaria parasite Plosmodium chabaudi chabaudi, grown in the presence of increasing concentrations of ART or ATN, showed 15-fold and 6-fold increased resistance to ART and ATN, respectively. Resistance remained stable after cloning, freeze-thawing, after passage in the absence of drug, and transmission through mosquitoes. The nucleotide sequences of the possible genetic modulators of ART resistance (mdr1, cg10, tctp, and atp6) of sensitive and resistant parasites were compared. No mutations in these genes were identified. In addition we investigated whether changes in the copy number of these genes could account for resistance but found that resistant parasites retained the same number of copies as their sensitive progenitors. We believe that this is the first report of a malaria parasite with genetically stable and transmissible resistance to artemisinin or its derivatives.

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A cornucopia of research resources for the fourth rodent malaria parasite species

BMC Biology ◽

10.1186/s12915-021-01019-y ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Jane M. Carlton

Keyword(s):

Malaria Parasite ◽

Parasite Species ◽

First Century ◽

Model Systems ◽

Rodent Malaria Parasite ◽

Malaria Parasites ◽

Rodent Malaria ◽

Human Malaria ◽

Plasmodium Vinckei ◽

Research Resources

AbstractThe study of human malaria caused by species of Plasmodium has undoubtedly been enriched by the use of model systems, such as the rodent malaria parasites originally isolated from African thicket rats. A significant gap in the arsenal of resources of the species that make up the rodent malaria parasites has been the lack of any such tools for the fourth of the species, Plasmodium vinckei. This has recently been rectified by Abhinay Ramaprasad and colleagues, whose pivotal paper published in BMC Biology describes a cornucopia of new P. vinckei ‘omics datasets, mosquito transmission experiments, transfection protocols, and virulence phenotypes, to propel this species firmly into the twenty-first century.

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Sex ratios in the rodent malaria parasite, Plasmodium chabaudi

Parasitology ◽

10.1017/s0031182003004013 ◽

2003 ◽

Vol 127 (5) ◽

pp. 419-425 ◽

Cited By ~ 26

Author(s):

S. E. REECE ◽

A. B. DUNCAN ◽

S. A. WEST ◽

A. F. READ

Keyword(s):

Mortality Rate ◽

Sex Ratio ◽

Malaria Parasite ◽

Sex Ratios ◽

Plasmodium Chabaudi ◽

Rodent Malaria Parasite ◽

Malaria Parasites ◽

Rodent Malaria ◽

Sex Ratio Theory

The sex ratios of malaria and related Apicomplexan parasites play a major role in transmission success. Here, we address 2 fundamental issues in the sex ratios of the rodent malaria parasite, Plasmodium chabaudi. First we test the accuracy of empirical methods for estimating sex ratios in malaria parasites, and show that sex ratios made with standard thin smears may overestimate the proportion of female gametocytes. Secondly, we test whether the mortality rate differs between male and female gametocytes, as assumed by sex ratio theory. Conventional application of sex ratio theory to malaria parasites assumes that the primary sex ratio can be accurately determined from mature gametocytes circulating in the peripheral circulation. We stopped gametocyte production with chloroquine in order to study a cohort of gametocytes in vitro. The mortality rate was significantly higher for female gametocytes, with an average half-life of 8 h for female gametocytes and 16 h for male gametocytes.

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Genome sequence, transcriptome, and annotation of rodent malaria parasite Plasmodium yoelii nigeriensis N67

BMC Genomics ◽

10.1186/s12864-021-07555-9 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Cui Zhang ◽

Cihan Oguz ◽

Sue Huse ◽

Lu Xia ◽

Jian Wu ◽

...

Keyword(s):

Dna Sequences ◽

Malaria Parasite ◽

Vaccine Development ◽

De Novo ◽

Gene Families ◽

Plasmodium Yoelii ◽

Control Measures ◽

Effective Control ◽

Malaria Parasites ◽

Rodent Malaria

Abstract Background Rodent malaria parasites are important models for studying host-malaria parasite interactions such as host immune response, mechanisms of parasite evasion of host killing, and vaccine development. One of the rodent malaria parasites is Plasmodium yoelii, and multiple P. yoelii strains or subspecies that cause different disease phenotypes have been widely employed in various studies. The genomes and transcriptomes of several P. yoelii strains have been analyzed and annotated, including the lethal strains of P. y. yoelii YM (or 17XL) and non-lethal strains of P. y. yoelii 17XNL/17X. Genomic DNA sequences and cDNA reads from another subspecies P. y. nigeriensis N67 have been reported for studies of genetic polymorphisms and parasite response to drugs, but its genome has not been assembled and annotated. Results We performed genome sequencing of the N67 parasite using the PacBio long-read sequencing technology, de novo assembled its genome and transcriptome, and predicted 5383 genes with high overall annotation quality. Comparison of the annotated genome of the N67 parasite with those of YM and 17X parasites revealed a set of genes with N67-specific orthology, expansion of gene families, particularly the homologs of the Plasmodium chabaudi erythrocyte membrane antigen, large numbers of SNPs and indels, and proteins predicted to interact with host immune responses based on their functional domains. Conclusions The genomes of N67 and 17X parasites are highly diverse, having approximately one polymorphic site per 50 base pairs of DNA. The annotated N67 genome and transcriptome provide searchable databases for fast retrieval of genes and proteins, which will greatly facilitate our efforts in studying the parasite biology and gene function and in developing effective control measures against malaria.

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