Intimate Molecular Interactions of <i>P. falciparum</i> Merozoite Proteins Involved in Invasion of Red Blood Cells and Their Implications for Vaccine Design

Rodrı́guez, Luis E.; Curtidor, Hernando; Urquiza, Mauricio; Cifuentes, Gladys; Reyes, Claudia; Patarroyo, Manuel E.

doi:10.1021/cr068407v

Cited by 85 publications

(85 citation statements)

References 444 publications

(1,524 reference statements)

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“…Of further interest, the NLR(N/K)(A/G) peptide shared by the six ORFs of P. falciparum is situated within a highly active binding peptide (Rodriguez et al, 2008), thought to interact with a glycoprotein-like receptor on the erythrocyte surface. Regardless of this intriguing similarity, it is unlikely that these five amino acids are sufficient evidence for a common evolutionary origin for all MSP3 proteins.…”

Section: Resultsmentioning

confidence: 99%

The origin and diversification of the merozoite surface protein 3 (msp3) multi-gene family in Plasmodium vivax and related parasites

Rice

Acosta

Pacheco

et al. 2014

Molecular Phylogenetics and Evolution

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The genus Plasmodium is a diversified group of parasites with more than 200 known species that includes those causing malaria in humans. These parasites use numerous proteins in a complex process that allows them to invade the red blood cells of their vertebrate hosts. Many of those proteins are part of multi-gene families; one of which is the merozoite surface protein-3 (msp3) family. The msp3 multi-gene family is considered important in the two main human parasites, Plasmodium vivax and Plasmodium falciparum, as its paralogs are simultaneously expressed in the blood stage (merozoite) and are immunogenic. There are large differences among Plasmodium species in the number of paralogs in this family. Such differences have been previously explained, in part, as adaptations that allow the different Plasmodium species to invade their hosts. To investigate this, we characterized the array containing msp3 genes among several Plasmodium species, including P. falciparum and P. vivax. We first found no evidence indicating that the msp3 family of P. falciparum was homologous to that of P. vivax. Subsequently, by focusing on the diverse clade of nonhuman primate parasites to which P. vivax is closely related, where homology was evident, we found no evidence indicating that the interspecies variation in the number of paralogs was an adaptation related to changes in host range or host switches. Overall, we hypothesize that the evolution of the msp3 family in P. vivax is consistent with a model of multi-allelic diversifying selection where the paralogs may have functionally redundant roles in terms of increasing antigenic diversity. Thus, we suggest that the expressed MSP3 proteins could serve as “decoys”, via antigenic diversity, during the critical process of invading the host red blood cells.

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Section: Resultsmentioning

confidence: 99%

The origin and diversification of the merozoite surface protein 3 (msp3) multi-gene family in Plasmodium vivax and related parasites

Rice

Acosta

Pacheco

et al. 2014

Molecular Phylogenetics and Evolution

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“…Like other repetitive proteins in Plasmodium spp. (Rodriguez et al, 2008), Pv MSP-9 has extensive polymorphism in the number of motifs; however, when the repetitive motifs are aligned among them (see Rich et al, 1997) the motifs themselves accumulate more synonymous than non-synonymous substitutions (Table 4). These repeated structures in proteins often occur in linear arrays or as a superhelix (Andrade et al, 2001) such as in MSP-9.…”

Section: Discussionmentioning

confidence: 99%

The evolution and diversity of a low complexity vaccine candidate, merozoite surface protein 9 (MSP-9), in Plasmodium vivax and closely related species

Chenet

Pacheco

Bacon

et al. 2013

Infection, Genetics and Evolution

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The merozoite surface protein-9 (MSP-9) has been considered a target for an anti-malarial vaccine since it is one of many proteins involved in the erythrocyte invasion, a critical step in the parasite life cycle. Orthologs encoding this antigen have been found in all known species of Plasmodium parasitic to primates. In order to characterize and investigate the extent and maintenance of msp-9 genetic diversity, we analyzed DNA sequences of the following malaria parasite species: Plasmodium falciparum, P. reichenowi, P. chabaudi, P. yoelii, P. berghei, P. coatneyi, P. gonderi, P. knowlesi, P. inui, P. simiovale, P. fieldi, P. cynomolgi and P. vivax and evaluated the signature of natural selection in all msp-9 orthologs. Our findings suggest that the gene encoding MSP-9 is under purifying selection in Plasmodium vivax and closely related species. We further explored how selection affected different regions of MSP-9 by comparing the polymorphisms in P. vivax and P. falciparum, and found contrasting patterns between these two species that suggest differences in functional constraints. This observation implies that the MSP-9 orthologs in human parasites may interact differently with the host immune response. Thus, studies carried out in one species cannot be directly translated into the other.

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“…In the search for high activity binding peptides as anti-malarial vaccine candidates (Patarroyo and Patarroyo, 2008; Rodriguez et al, 2008) it was found that peptide 20628 caused the lysis of human RBC (10.4% at 200 μM) (unpublished data). Peptide 20628 did not inhibit Gram-negative ( E. coli ATCC 25922) or Gram-positive ( S. aureus ATCC 29213) bacterial growth whilst its analog 35409 (K331A) had reduced hemolytic activity and inhibited E. coli and S. aureus bacterial growth (Maya, 2009).…”

Section: Introductionmentioning

confidence: 99%

A New Synthetic Peptide Having Two Target of Antibacterial Action in E. coli ML35

et al. 2016

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The increased resistance of microorganisms to the different antimicrobials available to today has highlighted the need to find new therapeutic agents, including natural and/or synthetic antimicrobial peptides (AMPs). This study has evaluated the antimicrobial activity of synthetic peptide 35409 (RYRRKKKMKKALQYIKLLKE) against Staphylococcus aureus ATCC 29213, Pseudomonas aeruginosa ATCC 15442 and Escherichia coli ML 35 (ATCC 43827). The results have shown that peptide 35409 inhibited the growth of these three bacterial strains, having 16-fold greater activity against E. coli and P. aeruginosa, but requiring less concentration regarding E. coli (22 μM). When analyzing this activity against E. coli compared to time taken, it was found that this peptide inhibited bacterial growth during the first 60 min and reduced CFU/mL 1 log after 120 min had elapsed. This AMP permeabilized the E. coli membrane by interaction with membrane phospholipids, mainly phosphatidylethanolamine, inhibited cell division and induced filamentation, suggesting two different targets of action within a bacterial cell. Cytotoxicity studies revealed that peptide 35409 had low hemolytic activity and was not cytotoxic for two human cell lines. We would thus propose, in the light of these findings, that the peptide 35409 sequence should provide a promising template for designing broad-spectrum AMPs.

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Intimate Molecular Interactions of P. falciparum Merozoite Proteins Involved in Invasion of Red Blood Cells and Their Implications for Vaccine Design

Cited by 85 publications

References 444 publications

The origin and diversification of the merozoite surface protein 3 (msp3) multi-gene family in Plasmodium vivax and related parasites

The origin and diversification of the merozoite surface protein 3 (msp3) multi-gene family in Plasmodium vivax and related parasites

The evolution and diversity of a low complexity vaccine candidate, merozoite surface protein 9 (MSP-9), in Plasmodium vivax and closely related species

A New Synthetic Peptide Having Two Target of Antibacterial Action in E. coli ML35

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