Ancient human sialic acid variant restricts an emerging zoonotic malaria parasite

Dankwa, Selasi; Lim, Caeul; Bei, Amy K.; Jiang, Rays H. Y.; Abshire, James Robbins; Patel, Shalin; Goldberg, Jonathan M.; Moreno, Yovany; Kono, Maya; Niles, Jacquin C.; Duraisingh, Manoj T.

doi:10.1038/ncomms11187

Cited by 52 publications

(75 citation statements)

References 67 publications

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“…duplication also occurred in the P. falciparum Multi Drug Resistance 1 (MDR1) gene under pressure from mefloquine (34,35). In another human infecting parasite Plasmodium knowlesi, duplication of DBPα, the Duffy blood group binding protein, occurred when the parasite was adapted to grow in human erythrocytes (36).…”

Section: Discussionmentioning

confidence: 99%

Role of Plasmodium vivax Duffy-binding protein 1 in invasion of Duffy-null Africans

Gunalan

Hostetler

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

121

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The ability of the malaria parasite Plasmodium vivax to invade erythrocytes is dependent on the expression of the Duffy blood group antigen on erythrocytes. Consequently, Africans who are null for the Duffy antigen are not susceptible to P. vivax infections. Recently, P. vivax infections in Duffy-null Africans have been documented, raising the possibility that P. vivax, a virulent pathogen in other parts of the world, may expand malarial disease in Africa. P. vivax binds the Duffy blood group antigen through its Duffy-binding protein 1 (DBP1). To determine if mutations in DBP1 resulted in the ability of P. vivax to bind Duffy-null erythrocytes, we analyzed P. vivax parasites obtained from two Duffy-null individuals living in Ethiopia where Duffy-null and -positive Africans live side-by-side. We determined that, although the DBP1s from these parasites contained unique sequences, they failed to bind Duffy-null erythrocytes, indicating that mutations in DBP1 did not account for the ability of P. vivax to infect Duffy-null Africans. However, an unusual DNA expansion of DBP1 (three and eight copies) in the two Duffy-null P. vivax infections suggests that an expansion of DBP1 may have been selected to allow low-affinity binding to another receptor on Duffy-null erythrocytes. Indeed, we show that Salvador (Sal) I P. vivax infects Squirrel monkeys independently of DBP1 binding to Squirrel monkey erythrocytes. We conclude that P. vivax Sal I and perhaps P. vivax in Duffy-null patients may have adapted to use new ligand-receptor pairs for invasion.Plasmodium vivax | Duffy blood group antigen | Duffy-binding protein | DNA expansionI n 1975 we identified the failure of Plasmodium knowlesi to invade Duffy-null erythrocytes (1). We assumed that the Duffy blood group null phenotype, a common African phenotype, conferred resistance in Africans to P. vivax, a Plasmodium closely related to P. knowlesi. Subsequent studies demonstrated that African American volunteers who were Duffy-null were resistant to mosquito-transmitted P. vivax (2). In addition, African American soldiers in Vietnam who were infected with P. vivax were all Duffypositive (3). Furthermore, African Americans in a village in Honduras who were infected with P. vivax were all Duffy-positive whereas those infected with P. falciparum were both Duffy-null and -positive (4). We concluded that Duffy null was the basis of resistance to P. vivax by Africans.The molecular basis of Duffy null was a single point mutation in the GATA1-binding sequence in the promotor region 5′ to the Duffy blood group ORF (Fig. 1B) that led to Duffy-blood-groupnull erythrocytes (5). In vitro studies with P. knowlesi demonstrated that the invasive merozoites were able to bind and reorient apically with Duffy-null erythrocytes but could not form a junction as occurred in Duffy-positive erythrocytes, indicating that the Duffy blood group was required for P. vivax invasion (6). Later, in P. knowlesi parasite culture supernatants, the parasite ligand binding to Duffy blood group antigen was identi...

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Section: Discussionmentioning

confidence: 99%

Role of Plasmodium vivax Duffy-binding protein 1 in invasion of Duffy-null Africans

Gunalan

Hostetler

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

121

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“…The F-pilus mediated glycan-dependent binding of uropathogenic Escherichia coli accounts for millions of urinary tract infections a year (720)(721) and small molecule inhibitors are being explored as therapies or prophylactics (722). With regard to parasites, a well-known example is the merozoite stage of Plasmodium falciparum, which initiates malaria via recognition of densely sialylated glycophorins on target erythrocytes (723)(724)(725)(726)(727)(728)(729)(730), with the types of sialic acids presented affecting species specificity (731)(732)(733). At a later stage in malaria, heparan sulfate on endothelial cells mediates the binding of P. falciparum-infected erythrocytes via the DBL1ɑ domain of PfEMP1 (734), likely accounting for some of the most serious complications of the disease.…”

Section: Bacterial Fungal and Parasite Adhesinsmentioning

confidence: 99%

Biological roles of glycans

2016

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Simple and complex carbohydrates (glycans) have long been known to play major metabolic, structural and physical roles in biological systems. Targeted microbial binding to host glycans has also been studied for decades. But such biological roles can only explain some of the remarkable complexity and organismal diversity of glycans in nature. Reviewing the subject about two decades ago, one could find very few clear-cut instances of glycan-recognition-specific biological roles of glycans that were of intrinsic value to the organism expressing them. In striking contrast there is now a profusion of examples, such that this updated review cannot be comprehensive. Instead, a historical overview is presented, broad principles outlined and a few examples cited, representing diverse types of roles, mediated by various glycan classes, in different evolutionary lineages. What remains unchanged is the fact that while all theories regarding biological roles of glycans are supported by compelling evidence, exceptions to each can be found. In retrospect, this is not surprising. Complex and diverse glycans appear to be ubiquitous to all cells in nature, and essential to all life forms. Thus, >3 billion years of evolution consistently generated organisms that use these molecules for many key biological roles, even while sometimes coopting them for minor functions. In this respect, glycans are no different from other major macromolecular building blocks of life (nucleic acids, proteins and lipids), simply more rapidly evolving and complex. It is time for the diverse functional roles of glycans to be fully incorporated into the mainstream of biological sciences.

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“…[42] expressed the functional chimpanzee CMAH gene in human hematopoietic stem cells. Comparison of human cells expressing Neu5Ac to those expressing Neu5Gc revealed that the presence of the latter strongly enhances P. knowlesi invasion.…”

Section: Monkey In the Middle: The Emerging Public Health Threat Posementioning

confidence: 99%

“…Nevertheless, Dankwa et al . [42] also suggest that P. knowlesi invasion and replication is less efficient in human cells relative to macaque cells, indicating that further adaptation may be necessary for widespread emergence.…”

Section: Monkey In the Middle: The Emerging Public Health Threat Posementioning

confidence: 99%

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Molecular interactions governing host-specificity of blood stage malaria parasites

Scully

Kanjee

Duraisingh

2017

Current Opinion in Microbiology

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Non-human primates harbor diverse species of malaria parasites, including the progenitors of P. falciparum and P. vivax. Cross-species transmission of some malaria parasites—most notably the macaque parasite, P. knowlesi—continues to this day, compelling the scientific community to ask whether these zoonoses could impede malaria control efforts by acting as a source of recurrent human infection. Host-restriction varies considerably among parasite species and is governed by both ecological and molecular variables. In particular, the efficiency of red blood cell invasion constitutes a prominent barrier to zoonotic emergence. Although proteins expressed upon the erythrocyte surface exhibit considerable diversity both within and among hosts, malaria parasites have adapted to this heterogeneity via the expansion of protein families associated with invasion, offering redundant mechanisms of host cell entry. This molecular toolkit may enable some parasites to circumvent host barriers, potentially yielding host shifts upon subsequent adaptation. Recent studies have begun to elucidate the molecular determinants of host-specificity, as well as the mechanisms that malaria parasites use to overcome these restrictions. We review recent studies concerning host tropism in the context of erythrocyte invasion by focusing on three malaria parasites that span the zoonotic spectrum: P. falciparum, P. knowlesi, and P. vivax.

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Ancient human sialic acid variant restricts an emerging zoonotic malaria parasite

Cited by 52 publications

References 67 publications

Role of Plasmodium vivax Duffy-binding protein 1 in invasion of Duffy-null Africans

Role of Plasmodium vivax Duffy-binding protein 1 in invasion of Duffy-null Africans

Biological roles of glycans

Molecular interactions governing host-specificity of blood stage malaria parasites

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