How selection forces dictate the variant surface antigens used by malaria parasites

Red blood cells infected by the malaria parasite Plasmodium falciparum express variant surface antigens (VSAs) that evade host immunity and allow the parasites to persist in the human population. There exist many different VSAs and the differential expression of these VSAs is associated with the virulence (damage to the host) of the parasites. The aim of this study is to unravel the differences in the effect key selection forces have on parasites expressing different VSAs such that we can better understand how VSAs enable the parasites to adapt to changes in their environment (like control measures) and how this may impact the virulence of the circulating parasites. To this end, we have built an individual-based model that captures the main selective forces on malaria parasites, namely parasite competition, host immunity, host death and mosquito abundance at both the within- and between-host levels. VSAs are defined by the net growth rates they infer to the parasites and the model keeps track of the expression of, and antibody build-up against, each VSA in all hosts. Our results show an ordered acquisition of VSA-specific antibodies with host age, which causes a dichotomy between the more virulent VSAs that reach high parasitaemias but are restricted to young relatively non-immune hosts, and less virulent VSAs that do not reach such high parasitaemias but can infect a wider range of hosts. The outcome of a change in the parasite's environment in terms of parasite virulence depends on the exact balance between the selection forces, which sets the limiting factor for parasite survival. Parasites will evolve towards expressing more virulent VSAs when the limiting factor for parasite survival is the within-host parasite growth and the parasites are able to minimize this limitation by expressing more virulent VSAs.

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Variant surface antigens of malaria parasites: functional and evolutionary insights from comparative gene family classification and analysis

BMC Genomics ◽

10.1186/1471-2164-14-427 ◽

2013 ◽

Vol 14 (1) ◽

pp. 427 ◽

Cited By ~ 45

Author(s):

Christian Frech ◽

Nansheng Chen

Keyword(s):

Gene Family ◽

Surface Antigens ◽

Malaria Parasites ◽

Variant Surface Antigens ◽

Family Classification

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Modulation of host cell receptors: a mechanism for the survival of malaria parasites

Parasitology ◽

10.1017/s0031182097002345 ◽

1997 ◽

Vol 115 (7) ◽

pp. 45-54 ◽

Cited By ~ 6

Author(s):

M. HOMMEL

Keyword(s):

Endothelial Cells ◽

Host Cell ◽

Surface Antigens ◽

Host Immunity ◽

Host Cells ◽

Microvascular Endothelial Cells ◽

Adhesion Receptors ◽

Malaria Parasites ◽

Cell Receptors ◽

Working Hypothesis

Intra-erythrocytic stages of malaria parasites can alter the surface of their host cells and release toxins which induce the production of cytokines, which in turn can up- or down-regulate the expression of adhesion receptors on the surface of microvascular endothelial cells. New adhesion receptors on endothelial cells provide the parasite with increased chances of survival despite an increasing level of host immunity. In order to take advantage of these new opportunities for survival, the parasite itself needs to make best use of its considerable ability to vary its surface antigens and adherent molecules. The paper describes the various players in this survival game and articulates a working hypothesis to explain how it may all fit together.

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Antigenic variation of cloned Plasmodium fragile in its natural host Macaca sinica. Sequential appearance of successive variant antigenic types.

Journal of Experimental Medicine ◽

10.1084/jem.165.5.1269 ◽

1987 ◽

Vol 165 (5) ◽

pp. 1269-1283 ◽

Cited By ~ 84

Author(s):

S M Handunnetti ◽

K N Mendis ◽

P H David

Keyword(s):

Developmental Stages ◽

Antigenic Variation ◽

Surface Antigens ◽

Immune Serum ◽

Natural Host ◽

Variant Surface Antigens ◽

Parasite Survival ◽

Macaca Sinica ◽

Antigenic Type ◽

Sequential Appearance

The course of infection of Plasmodium fragile in its natural host, the toque monkey Macaca sinica, consists of a primary peak of parasitemia followed by several distinct, successive peaks of lower parasitemia. In the S+ host, the late intraerythrocytic asexual developmental stages of P. fragile induce the expression of antigens on the surface of infected erythrocytes, which could be detected using the technique of surface immunofluorescence. Immunofluorescence using unfixed erythrocytes in suspension has shown that antigens are recognized by immune serum on the surface of the erythrocytes infected with more mature stages of the parasite. These antigens undergo variation, each successive peak of parasitemia being characterized by a different variant antigenic type (VAT). The appearance of the successive VATs occurs in a sequential manner, following the same order in different sets of animals. This constitutes the first example of a sequential expression of antigens in a malaria parasite; it indicates that, in P. fragile, antigenic variation is not the result of random mutations selected by antibody. Parasite-induced antigens on the surface of infected erythrocytes could not be detected in the S- host. However, when nonexpressing parasites from the S- host were transferred by blood passage into a naive S+ animal, they began to express antigens on the surface of infected erythrocytes within two erythrocytic cycles. We have demonstrated that the ability of S- parasites to switch to a particular VAT when passaged into a S+ animal changes during the course of an infection in the S- animal, indicating that, although surface antigens are not expressed, the processes leading to antigenic variation occurs even in the S- host. Antibodies directed against these surface antigens inhibit the growth of intra-erythrocytic parasites. The growth inhibition effects of antibodies are also variant specific, indicating that these variant surface antigens are functionally important for parasite survival.

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Faculty Opinions recommendation of Escape of malaria parasites from host immunity requires CD4+ CD25+ regulatory T cells.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1016854.210426 ◽

2004 ◽

Author(s):

Michael Good

Keyword(s):

T Cells ◽

Regulatory T Cells ◽

Host Immunity ◽

Malaria Parasites

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Microbiome-based environmental monitoring of a dairy processing facility highlights the challenges associated with low microbial-load samples

npj Science of Food ◽

10.1038/s41538-021-00087-2 ◽

2021 ◽

Vol 5 (1) ◽

Author(s):

Aoife J. McHugh ◽

Min Yap ◽

Fiona Crispie ◽

Conor Feehily ◽

Colin Hill ◽

...

Keyword(s):

Environmental Monitoring ◽

Illumina Sequencing ◽

Food Chain ◽

Control Measures ◽

Initial Assessment ◽

Limiting Factor ◽

Accurate Identification ◽

Processing Facility ◽

High Concentrations ◽

Sequencing Platforms

AbstractEfficient and accurate identification of microorganisms throughout the food chain can potentially allow the identification of sources of contamination and the timely implementation of control measures. High throughput DNA sequencing represents a potential means through which microbial monitoring can be enhanced. While Illumina sequencing platforms are most typically used, newer portable platforms, such as the Oxford Nanopore Technologies (ONT) MinION, offer the potential for rapid analysis of food chain microbiomes. Initial assessment of the ability of rapid MinION-based sequencing to identify microbes within a simple mock metagenomic mixture is performed. Subsequently, we compare the performance of both ONT and Illumina sequencing for environmental monitoring of an active food processing facility. Overall, ONT MinION sequencing provides accurate classification to species level, comparable to Illumina-derived outputs. However, while the MinION-based approach provides a means of easy library preparations and portability, the high concentrations of DNA needed is a limiting factor.

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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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An afebrile heartwater-like syndrome in goats

Journal of the South African Veterinary Association ◽

10.4102/jsava.v84i1.955 ◽

2013 ◽

Vol 84 (1) ◽

Author(s):

Rhoda Leask ◽

Kenneth P. Pettey ◽

Gareth F. Bath

Keyword(s):

Clinical Signs ◽

Control Measures ◽

Sub Saharan Africa ◽

Limiting Factor ◽

Febrile Reaction ◽

Presumptive Diagnosis ◽

Appropriate Treatment ◽

Sub Saharan ◽

Characteristic Features ◽

And Control

Heartwater is a serious limiting factor for sheep and goat production in the major endemic area of sub-Saharan Africa and therefore most knowledge, research and control methods originate from this region. Whilst the usual or common clinical presentations can be used to make a presumptive diagnosis of heartwater with a good measure of confidence, this is not always the case, and animals suffering from heartwater may be misdiagnosed because their cases do not conform to the expected syndrome, signs and lesions. One aberrant form found occasionally in the Channel Island breeds of cattle and some goats is an afebrile heartwaterlike syndrome. The most constant and characteristic features of this heartwater-like syndrome comprise normal temperature, clinical signs associated with generalised oedema, and nervous signs, especially hypersensitivity. The presumption that the disease under investigation is the afebrile heartwater-like syndrome entails a tentative diagnosis based on history and clinical signs and the response to presumed appropriate treatment (metadiagnosis). The afebrile heartwater-like syndrome presents similarly to peracute heartwater but without the febrile reaction. Peracute cases of heartwater have a high mortality rate, enabling confirmation of the disease on post-mortem examination. Recognition of the afebrile heartwater-like syndrome is important to prevent deaths and identify the need for appropriate control measures.

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