The Role of Serine-Type Serine Repeat Antigen in Plasmodium yoelii Blood Stage Development

Huang, Xiucai; Liew, K. M.; Natalang, Onguma; Siau, Anthony; Zhang, Neng; Preiser, Peter R.

doi:10.1371/journal.pone.0060723

Cited by 10 publications

(14 citation statements)

References 34 publications

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“…Among organisms in the apicomplexan phylum and with the exception of Theileria found in cattle, species of Plasmodium are the only organisms that the gene family translating into Serine-repeat antigen (SERA) protein has been found [55]. This protein was found in 1 sample.…”

Section: Discussionmentioning

confidence: 99%

Proteomic analysis of microparticles isolated from malaria positive blood samples

et al. 2016

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BackgroundMalaria continues to be a great public health concern due to the significant mortality and morbidity associated with the disease especially in developing countries. Microparticles (MPs), also called plasma membrane derived extracellular vesicles (PMEVs) are subcellular structures that are generated when they bud off the plasma membrane. They can be found in healthy individuals but the numbers tend to increase in pathological conditions including malaria. Although, various studies have been carried out on the protein content of specific cellular derived MPs, there seems to be paucity of information on the protein content of circulating MPs in malaria and their association with the various signs and symptoms of the disease. The aim of this study was therefore to carry out proteomic analyses of MPs isolated from malaria positive samples and compare them with proteins of MPs from malaria parasite culture supernatant and healthy controls in order to ascertain the role of MPs in malaria infection.MethodsPlasma samples were obtained from forty-three (43) malaria diagnosed patients (cases) and ten (10) healthy individuals (controls). Malaria parasite culture supernatant was obtained from our laboratory and MPs were isolated from them and confirmed using flow cytometry. 2D LC-MS was done to obtain their protein content. Resultant data were analyzed using SPSS Ver. 21.0 statistical software, Kruskal Wallis test and Spearman’s correlation coefficient r.ResultsIn all, 1806 proteins were isolated from the samples. The MPs from malaria positive samples recorded 1729 proteins, those from culture supernatant were 333 while the control samples recorded 234 proteins. The mean number of proteins in MPs of malaria positive samples was significantly higher than that in the control samples. Significantly, higher quantities of haemoglobin subunits were seen in MPs from malaria samples and culture supernatant compared to control samples.ConclusionA great number of proteins were observed to be carried in the microparticles (MPs) from malaria samples and culture supernatant compared to controls. The greater loss of haemoglobin from erythrocytes via MPs from malaria patients could serve as the initiation and progression of anaemia in P.falciparum infection. Also while some proteins were upregulated in circulating MPs in malaria samples, others were down regulated.

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Section: Discussionmentioning

confidence: 99%

Proteomic analysis of microparticles isolated from malaria positive blood samples

et al. 2016

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“…In P. berghei, simultaneous disruption of the two Group IV sera genes, Pb-sera1 and Pb-sera2, did not affect parasite growth [56], suggesting nonessential or auxillary roles. Similarly, disruption of Plasmodium yoelii (Py)-sera1 and Py-sera2, which showed higher transcription levels in virulent compared to avirulent parasite lines, did not affect parasite survival in vivo, although the lethality of the parasite was attenuated [57]. In contrast, Pf-SERA5 is essential for P. falciparum growth [22,27,[32][33][34].…”

Section: Polymorphism Of Sera Genesmentioning

confidence: 99%

Characteristic features of the SERA multigene family in the malaria parasite

et al. 2020

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Serine repeat antigen (SERA) is conserved among species of the genus Plasmodium. Sera genes form a multigene family and are generally tandemly clustered on a single chromosome. Although all Plasmodium species encode multiple sera genes, the number varies between species. Among species, the members share similar sequences and gene organization. SERA possess a central papain-like cysteine protease domain, however, in some members, the active site cysteine residue is substituted with a serine. Recent studies implicate this gene family in a number of aspects in parasite biology and induction of protective immune response. This review summarizes the current understanding on this important gene family in several Plasmodium species. The Plasmodium falciparum (Pf)-sera family, for example, consists of nine gene members. Unlike other multigene families in Plasmodium species, Pf-sera genes do not exhibit antigenic variation. Pf-sera5 nucleotide diversity is also low. Moreover, although Pf-sera5 is highly transcribed during the blood stage of malaria infection, and a large amount is released into the host blood following schizont rupture, in malaria endemic countries the sero-positive rates for Pf-SERA5 are low, likely due to Pf-SERA5 binding of host proteins to avoid immune recognition. As an antigen, the N-terminal 47 kDa domain of Pf-SERA5 is a promising vaccine candidate currently undergoing clinical trials. Pf-SERA5 and Pf-SERA6, as well as P. berghei (Pb)-SERA3, and Pb-SERA5, have been investigated for their roles in parasite egress. Two P. yoelii SERA, which have a serine residue at the protease active center, are implicated in parasite virulence. Overall, these studies provide insight that during the evolution of the Plasmodium parasite, the sera gene family members have increased by gene duplication, and acquired various functions that enable the parasite to survive and successfully maintain infection in the host.

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“…56 The SERAs are encoded from a multigene protease family, common to all Plasmodium species 57,58 but occurring in different types, from which the serine-type SERA SERA5 and cysteine-type SERA SERA6 show the highest levels in P. falciparum. 59,60 According to a recent study, SERA5 has been discussed to have no enzymatic role 61 during the blood-stage growth of P. falciparum, and although obviously regulating the kinetics and efficiency of malaria parasite invasion and egress from host erythrocytes, neither SERA5 function nor the role of its processing appear to be completely understood. 62 Nevertheless, in view of the strong susceptibility of the humans with blood group A to infection by P. falciparum, SERA5 is strongly suggested to function as an acceptor in enzyme-substrate competition between host and parasite in mucin-type O-GalNAc glycosylations.…”

Section: The Susceptibility Of Non-o Blood Group Individuals To the Imentioning

confidence: 99%

Position of human blood group O(H) and phenotype‐determining enzymes in growth and infectious disease

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Annals of the New York Academy of Sciences

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The human ABO(H) blood group phenotypes arise from the evolutionarily oldest genetic system found in primate populations. While the blood group antigen A is considered the ancestral primordial structure, under the selective pressure of life-threatening diseases blood group O(H) came to dominate as the most frequently occurring blood group worldwide. Non-O(H) phenotypes demonstrate impaired formation of adaptive and innate immunoglobulin specificities due to clonal selection and phenotype formation in plasma proteins. Compared with individuals with blood group O(H), blood group A individuals not only have a significantly higher risk of developing certain types of cancer but also exhibit high susceptibility to malaria tropica or infection by Plasmodium falciparum. The phenotype-determining blood group A glycotransferase(s), which affect the levels of anti-A/Tn cross-reactive immunoglobulins in phenotypic glycosidic accommodation, might also mediate adhesion and entry of the parasite to host cells via trans-species O-GalNAc glycosylation of abundantly expressed serine residues that arise throughout the parasite's life cycle, while excluding the possibility of antibody formation against the resulting hybrid Tn antigen. In contrast, human blood group O(H), lacking this enzyme, is indicated to confer a survival advantage regarding the overall risk of developing cancer, and individuals with this blood group rarely develop life-threatening infections involving evolutionarily selective malaria strains.

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The Role of Serine-Type Serine Repeat Antigen in Plasmodium yoelii Blood Stage Development

Cited by 10 publications

References 34 publications

Proteomic analysis of microparticles isolated from malaria positive blood samples

Proteomic analysis of microparticles isolated from malaria positive blood samples

Characteristic features of the SERA multigene family in the malaria parasite

Position of human blood group O(H) and phenotype‐determining enzymes in growth and infectious disease

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