Functional analysis of Plasmodium falciparum subpopulations associated with artemisinin resistance in Cambodia.

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Abstract

Plasmodium falciparum malaria is one of the most widespread parasitic infections in humans and remains a leading global health concern. Malaria elimination efforts are threatened by the emergence and spread of resistance to artemisinin-based combination therapy, the first-line treatment of malaria. Promising molecular markers and pathways associated with artemisinin drug resistance have been identified, but the underlying molecular mechanisms of resistance remains unknown. The genomic data from early period of emergence of artemisinin resistance (2008-2011) was evaluated, with aim to define k13 associated genetic background in Cambodia, the country identified as epicentre of anti-malarial drug resistance, through characterization of 167 parasite isolates using a panel of 21,257 SNPs.

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Most cited references 38

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The role of Atg proteins in autophagosome formation.

Noboru Mizushima, Tamotsu Yoshimori, Yoshinori Ohsumi (2011)

Macroautophagy is mediated by a unique organelle, the autophagosome, which encloses a portion of cytoplasm for delivery to the lysosome. Autophagosome formation is dynamically regulated by starvation and other stresses and involves complicated membrane reorganization. Since the discovery of yeast Atg-related proteins, autophagosome formation has been dissected at the molecular level. In this review we describe the molecular mechanism of autophagosome formation with particular focus on the function of Atg proteins and the long-standing discussion regarding the origin of the autophagosome membrane.

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Discovery of gene function by expression profiling of the malaria parasite life cycle.

Karine G Le Roch, Yingyao Zhou, Peter Blair … (2003)

The completion of the genome sequence for Plasmodium falciparum, the species responsible for most malaria human deaths, has the potential to reveal hundreds of new drug targets and proteins involved in pathogenesis. However, only approximately 35% of the genes code for proteins with an identifiable function. The absence of routine genetic tools for studying Plasmodium parasites suggests that this number is unlikely to change quickly if conventional serial methods are used to characterize encoded proteins. Here, we use a high-density oligonucleotide array to generate expression profiles of human and mosquito stages of the malaria parasite's life cycle. Genes with highly correlated levels and temporal patterns of expression were often involved in similar functions or cellular processes.

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Microsatellite markers reveal a spectrum of population structures in the malaria parasite Plasmodium falciparum.

T. J. Anderson, B Haubold, J T Williams … (2000)

Multilocus genotyping of microbial pathogens has revealed a range of population structures, with some bacteria showing extensive recombination and others showing almost complete clonality. The population structure of the protozoan parasite Plasmodium falciparum has been harder to evaluate, since most studies have used a limited number of antigen-encoding loci that are known to be under strong selection. We describe length variation at 12 microsatellite loci in 465 infections collected from 9 locations worldwide. These data reveal dramatic differences in parasite population structure in different locations. Strong linkage disequilibrium (LD) was observed in six of nine populations. Significant LD occurred in all locations with prevalence <1% and in only two of five of the populations from regions with higher transmission intensities. Where present, LD results largely from the presence of identical multilocus genotypes within populations, suggesting high levels of self-fertilization in populations with low levels of transmission. We also observed dramatic variation in diversity and geographical differentiation in different regions. Mean heterozygosities in South American countries (0.3-0.4) were less than half those observed in African locations (0. 76-0.8), with intermediate heterozygosities in the Southeast Asia/Pacific samples (0.51-0.65). Furthermore, variation was distributed among locations in South America (F:(ST) = 0.364) and within locations in Africa (F:(ST) = 0.007). The intraspecific patterns of diversity and genetic differentiation observed in P. falciparum are strikingly similar to those seen in interspecific comparisons of plants and animals with differing levels of outcrossing, suggesting that similar processes may be involved. The differences observed may also reflect the recent colonization of non-African populations from an African source, and the relative influences of epidemiology and population history are difficult to disentangle. These data reveal a range of population structures within a single pathogen species and suggest intimate links between patterns of epidemiology and genetic structure in this organism.

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Author and article information

Journal

Journal ID (iso-abbrev): Malar. J.

Title: Malaria journal

Publisher: Springer Science and Business Media LLC

ISSN (Electronic): 1475-2875

ISSN (Print): 1475-2875

Publication date (Electronic): Dec 19 2017

Volume: 16

Issue: 1

Affiliations

[1 ] Institut de Biologie Computationnelle (IBC), 34095, Montpellier, France. aankitddwivedi@gmail.com.

[2 ] Institut de Recherche en Cancérologie de Montpellier, Institut régional du Cancer Montpellier & Université de Montpellier, IRCM-INSERM U1194, 34298, Montpellier, France. aankitddwivedi@gmail.com.

[3 ] Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, 21201, USA. aankitddwivedi@gmail.com.

[4 ] Laboratoire de Biostatistiques, Informatique et Physique Pharmaceutique, UFR Pharmacie, Université de Montpellier, 34093, Montpellier, France.

[5 ] Institut de Génomique Fonctionnelle-CNRS, 34094, Montpellier, France.

[6 ] Institut de Recherche en Cancérologie de Montpellier, Institut régional du Cancer Montpellier & Université de Montpellier, IRCM-INSERM U1194, 34298, Montpellier, France.

[7 ] Institut de Biologie Computationnelle (IBC), 34095, Montpellier, France.

[8 ] Centre de Recherche en Biologie cellulaire de Montpellier, CNRS-UMR 5237, 34293, Montpellier, France.

[9 ] Malaria Molecular Epidemiology Unit, Institut Pasteur du Cambodge, Phnom Penh, Cambodia.

[10 ] Laboratoire d'informatique, de robotique et de microélectronique de Montpellier, LIRMM, CNRS, Université de Montpellier, 34095, Montpellier, France.

[11 ] Center for Integrative Medical Sciences, RIKEN, Yokohama, Kanagawa, Japan.

[12 ] CIRAD, UMR Intertryp, 34398, Montpellier, France.

[13 ] IES, UMR 5214, Université de Montpellier, CNRS, 34095, Montpellier, France.

[14 ] Biology of Host-Parasite Interactions Unit, Institut Pasteur, Paris, France.

[15 ] Section of Infectious Diseases, Department of Internal Medicine, Yale School of Medicine, New Haven, CT, 06520, USA.

[16 ] Institut de Biologie Computationnelle (IBC), 34095, Montpellier, France. emmanuel.cornillot@umontpellier.fr.

[17 ] Institut de Recherche en Cancérologie de Montpellier, Institut régional du Cancer Montpellier & Université de Montpellier, IRCM-INSERM U1194, 34298, Montpellier, France. emmanuel.cornillot@umontpellier.fr.

Article

Publisher Item ID: 10.1186/s12936-017-2140-1

DOI: 10.1186/s12936-017-2140-1

PMC ID: 5735551

PubMed ID: 29258508

SO-VID: 796fb5ad-b2df-48f3-9bfc-d2584970c854

History

Keywords: Shifting balance theory,k13,Admixed subpopulations,Artemisinin resistance,Cambodia,Malaria,Network based stratification,Plasmodium falciparum,Population fragmentation,Redox metabolism

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Keywords: Shifting balance theory, k13, Admixed subpopulations, Artemisinin resistance, Cambodia, Malaria, Network based stratification, Plasmodium falciparum, Population fragmentation, Redox metabolism

Functional analysis of Plasmodium falciparum subpopulations associated with artemisinin resistance in Cambodia.

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Abstract

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Malaria vaccine development

Most cited references 38

The role of Atg proteins in autophagosome formation.

Discovery of gene function by expression profiling of the malaria parasite life cycle.

Microsatellite markers reveal a spectrum of population structures in the malaria parasite Plasmodium falciparum.

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