Category: Genomics of Apicomplexa

Apr 08

DNA repair mechanisms and their biological roles in the malaria parasite Plasmodium falciparum.

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DNA repair mechanisms and their biological roles in the malaria parasite Plasmodium falciparum.
Microbiol Mol Biol Rev. 2014 Sep;78(3):469-86
Authors: Lee AH, Symington LS, Fidock DA
Abstra…

Apr 01

A population genetic model for the initial spread of partially resistant malaria parasites under anti-malarial combination therapy and weak intrahost competition.

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A population genetic model for the initial spread of partially resistant malaria parasites under anti-malarial combination therapy and weak intrahost competition.
PLoS One. 2014;9(7):e101601
Author…

Apr 01

An orthology-based analysis of pathogenic protozoa impacting global health: an improved comparative genomics approach with prokaryotes and model eukaryote orthologs.

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An orthology-based analysis of pathogenic protozoa impacting global health: an improved comparative genomics approach with prokaryotes and model eukaryote orthologs.

OMICS. 2014 Aug;18(8):524-38

Authors: Cuadrat RR, da Serra Cruz SM, Tschoeke DA, Silva E, Tosta F, Jucá H, Jardim R, Campos ML, Mattoso M, Dávila AM

Abstract
A key focus in 21(st) century integrative biology and drug discovery for neglected tropical and other diseases has been the use of BLAST-based computational methods for identification of orthologous groups in pathogenic organisms to discern orthologs, with a view to evaluate similarities and differences among species, and thus allow the transfer of annotation from known/curated proteins to new/non-annotated ones. We used here a profile-based sensitive methodology to identify distant homologs, coupled to the NCBI’s COG (Unicellular orthologs) and KOG (Eukaryote orthologs), permitting us to perform comparative genomics analyses on five protozoan genomes. OrthoSearch was used in five protozoan proteomes showing that 3901 and 7473 orthologs can be identified by comparison with COG and KOG proteomes, respectively. The core protozoa proteome inferred was 418 Protozoa-COG orthologous groups and 704 Protozoa-KOG orthologous groups: (i) 31.58% (132/418) belongs to the category J (translation, ribosomal structure, and biogenesis), and 9.81% (41/418) to the category O (post-translational modification, protein turnover, chaperones) using COG; (ii) 21.45% (151/704) belongs to the categories J, and 13.92% (98/704) to the O using KOG. The phylogenomic analysis showed four well-supported clades for Eukarya, discriminating Multicellular [(i) human, fly, plant and worm] and Unicellular [(ii) yeast, (iii) fungi, and (iv) protozoa] species. These encouraging results attest to the usefulness of the profile-based methodology for comparative genomics to accelerate semi-automatic re-annotation, especially of the protozoan proteomes. This approach may also lend itself for applications in global health, for example, in the case of novel drug target discovery against pathogenic organisms previously considered difficult to research with traditional drug discovery tools.

PMID: 24960463 [PubMed – indexed for MEDLINE]

Feb 20

Whole-genome scans provide evidence of adaptive evolution in Malawian Plasmodium falciparum isolates.

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Whole-genome scans provide evidence of adaptive evolution in Malawian Plasmodium falciparum isolates.

J Infect Dis. 2014 Dec 15;210(12):1991-2000

Authors: Ocholla H, Preston MD, Mipando M, Jensen AT, Campino S, MacInnis B, Alcock D, Terlouw A, Zongo I, Oudraogo JB, Djimde AA, Assefa S, Doumbo OK, Borrmann S, Nzila A, Marsh K, Fairhurst RM, Nosten F, Anderson TJ, Kwiatkowski DP, Craig A, Clark TG, Montgomery J

Abstract
BACKGROUND: Selection by host immunity and antimalarial drugs has driven extensive adaptive evolution in Plasmodium falciparum and continues to produce ever-changing landscapes of genetic variation.
METHODS: We performed whole-genome sequencing of 69 P. falciparum isolates from Malawi and used population genetics approaches to investigate genetic diversity and population structure and identify loci under selection.
RESULTS: High genetic diversity (π = 2.4 × 10(-4)), moderately high multiplicity of infection (2.7), and low linkage disequilibrium (500-bp) were observed in Chikhwawa District, Malawi, an area of high malaria transmission. Allele frequency-based tests provided evidence of recent population growth in Malawi and detected potential targets of host immunity and candidate vaccine antigens. Comparison of the sequence variation between isolates from Malawi and those from 5 geographically dispersed countries (Kenya, Burkina Faso, Mali, Cambodia, and Thailand) detected population genetic differences between Africa and Asia, within Southeast Asia, and within Africa. Haplotype-based tests of selection to sequence data from all 6 populations identified signals of directional selection at known drug-resistance loci, including pfcrt, pfdhps, pfmdr1, and pfgch1.
CONCLUSIONS: The sequence variations observed at drug-resistance loci reflect differences in each country’s historical use of antimalarial drugs and may be useful in formulating local malaria treatment guidelines.

PMID: 24948693 [PubMed – indexed for MEDLINE]

Feb 11

Origin of robustness in generating drug-resistant malaria parasites.

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Origin of robustness in generating drug-resistant malaria parasites.

Mol Biol Evol. 2014 Jul;31(7):1649-60

Authors: Kümpornsin K, Modchang C, Heinberg A, Ekland EH, Jirawatcharadech P, Chobson P, Suwanakitti N, Chaotheing S, Wilairat P, Deitsch KW, Kamchonwongpaisan S, Fidock DA, Kirkman LA, Yuthavong Y, Chookajorn T

Abstract
Biological robustness allows mutations to accumulate while maintaining functional phenotypes. Despite its crucial role in evolutionary processes, the mechanistic details of how robustness originates remain elusive. Using an evolutionary trajectory analysis approach, we demonstrate how robustness evolved in malaria parasites under selective pressure from an antimalarial drug inhibiting the folate synthesis pathway. A series of four nonsynonymous amino acid substitutions at the targeted enzyme, dihydrofolate reductase (DHFR), render the parasites highly resistant to the antifolate drug pyrimethamine. Nevertheless, the stepwise gain of these four dhfr mutations results in tradeoffs between pyrimethamine resistance and parasite fitness. Here, we report the epistatic interaction between dhfr mutations and amplification of the gene encoding the first upstream enzyme in the folate pathway, GTP cyclohydrolase I (GCH1). gch1 amplification confers low level pyrimethamine resistance and would thus be selected for by pyrimethamine treatment. Interestingly, the gch1 amplification can then be co-opted by the parasites because it reduces the cost of acquiring drug-resistant dhfr mutations downstream in the same metabolic pathway. The compensation of compromised fitness by extra GCH1 is an example of how robustness can evolve in a system and thus expand the accessibility of evolutionary trajectories leading toward highly resistant alleles. The evolution of robustness during the gain of drug-resistant mutations has broad implications for both the development of new drugs and molecular surveillance for resistance to existing drugs.

PMID: 24739308 [PubMed – indexed for MEDLINE]

Jan 22

Cryptosporidiosis in broiler chickens in Zhejiang Province, China: molecular characterization of oocysts detected in fecal samples.

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Cryptosporidiosis in broiler chickens in Zhejiang Province, China: molecular characterization of oocysts detected in fecal samples.
Parasite. 2014;21:36
Authors: Wang L, Xue X, Li J, Zhou Q, Yu Y,…

Jan 16

Molecular identification of the chitinase genes in Plasmodium relictum.

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Molecular identification of the chitinase genes in Plasmodium relictum.
Malar J. 2014;13:239
Authors: Garcia-Longoria L, Hellgren O, Bensch S
Abstract
BACKGROUND: Malaria parasites…

Oct 18

Survey of the parasite Toxoplasma gondii in human consumed ovine meat in Tunis City.

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Survey of the parasite Toxoplasma gondii in human consumed ovine meat in Tunis City.
PLoS One. 2014;9(1):e85044
Authors: Boughattas S, Ayari K, Sa T, Aoun K, Bouratbine A
Abstract

Sep 25

Outbreak of human infection with Sarcocystis nesbitti, Malaysia, 2012.

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Outbreak of human infection with Sarcocystis nesbitti, Malaysia, 2012.
Emerg Infect Dis. 2013 Dec;19(12):1989-91
Authors: Abubakar S, Teoh BT, Sam SS, Chang LY, Johari J, Hooi PS, Lakhbeer-Singh H…

Sep 25

Using mitochondrial genome sequences to track the origin of imported Plasmodium vivax infections diagnosed in the United States.

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Using mitochondrial genome sequences to track the origin of imported Plasmodium vivax infections diagnosed in the United States.
Am J Trop Med Hyg. 2014 Jun;90(6):1102-8
Authors: Rodrigues PT, Alve…