Mechanisms of genetically-based resistance to malaria

López, Carolina; Saravia, Carolina; Gómez, Alexander; Hoebeke, Johan; Patarroyo, Manuel A.

doi:10.1016/j.gene.2010.07.008

Cited by 134 publications

(115 citation statements)

References 163 publications

(229 reference statements)

Supporting

Mentioning

109

Contrasting

Unclassified

Order By: Relevance

“…Fortunately, in recent years there have been excellent reviews of the mechanisms of malaria resistance, as well as surveys of the many genes that may putatively confer malaria resistance (Kwiatkowski, 2005;Verra et al, 2009;Ló pez et al, 2010). Therefore, I will not discuss in detail the molecular basis of the mechanisms of resistance or enumerate all the potential malaria resistance genes, but will focus on the genetic variants in which there is strong evidence for resistance, and data useful for population genetic approaches and analysis.…”

Section: Haldane 1: I Agree With Dr Montalenti's Projectmentioning

confidence: 99%

Population genetics of malaria resistance in humans

2011

View full text Add to dashboard Cite

Section: Haldane 1: I Agree With Dr Montalenti's Projectmentioning

confidence: 99%

Population genetics of malaria resistance in humans

2011

View full text Add to dashboard Cite

“…The most prevalent genetically based resistance mechanisms are hemoglobinopathies such as thalassemia, sickle cell trait, and hemoglobin C, erythrocyte polymorphisms such as Duffy antigen and ovalocytosis, immunogenic variants such as in HLA alleles, nitric oxide synthase 1, and tumor necrosis factor a (reviewed in ref. 10), and enzymopathies including glucose-6-phosphate dehydrogenase (G6PD) deficiency (11). Another enzymopathy suggested to protect humans from malaria is the less common pyruvate kinase deficiency (12).…”

Section: Introductionmentioning

confidence: 99%

Glucose‐6‐phosphate metabolism in Plasmodium falciparum

2012

View full text Add to dashboard Cite

Malaria is still one of the most threatening diseases worldwide. The high drug resistance rates of malarial parasites make its eradication difficult and furthermore necessitate the development of new antimalarial drugs. Plasmodium falciparum is responsible for severe malaria and therefore of special interest with regard to drug development. Plasmodium parasites are highly dependent on glucose and very sensitive to oxidative stress; two observations that drew interest to the pentose phosphate pathway (PPP) with its key enzyme glucose‐6‐phosphate dehydrogenase (G6PD). A central position of the PPP for malaria parasites is supported by the fact that human G6PD deficiency protects to a certain degree from malaria infections. Plasmodium parasites and the human host possess a complete PPP, both of which seem to be important for the parasites. Interestingly, there are major differences between parasite and human G6PD, making the enzyme of Plasmodium a promising target for antimalarial drug design. This review gives an overview of the current state of research on glucose‐6‐phosphate metabolism in P. falciparum and its impact on malaria infections. Moreover, the unique characteristics of the enzyme G6PD in P. falciparum are discussed, upon which its current status as promising target for drug development is based. © 2012 IUBMB IUBMB Life, 64(7): 603–611, 2012

show abstract

“…In human beings the Duffy antigen aminoacid shifting G44D deϐines two phenotypes (Fy a and Fy b ) (Iwamoto et al, 1996) but does not confer any Plasmodium vivax resistance (Miller et al 1976); however, a single aminoacid substitution (R89C) reduces by 90% the level of Duffy protein detected on the erythrocytes (Olsson et al 1998, Tournamille et al 1998 which reduces it ability to bind to chemokines and therefore possibly might confer certain resistance to P. vivax infection (López et al 2010). The alignment of Bos taurus taurus and Bos taurus indicus Duffy protein sequences deposited at the GeneBank shows 99% identity and just the changes at the aminoacid 22 (F22L) are exclusive of Bos taurus indicus which could have a role in babesiosis resistance.…”

Section: Discussionmentioning

confidence: 99%

Detection and quantification of Duffy antigen on bovine red blood cell membranes using a polyclonal antibody

et al. 2012

View full text Add to dashboard Cite

Babesiosis is one of the most important diseases affecting livestock agriculture worldwide. Animals from the subspecies Bos taurus indicus are more resistant to babesiosis than those from Bos taurus taurus. The genera Babesia and Plasmodium are Apicomplexa hemoparasites and share features such as invasion of red blood cells (RBC). The glycoprotein Duffy is the only human erythrocyte receptor for Pasmodium vivax and a mutation which abolishes expression of this glycoprotein on erythrocyte surfaces is responsible for making the majority of people originating from the indigenous populations of West Africa resistant to P. vivax. The current work detected and quantified the Duffy antigen on Bos taurus indicus and Bos taurus taurus erythrocyte surfaces using a polyclonal antibody in order to investigate if differences in susceptibility to Babesia are due to different levels of Duffy antigen expression on the RBCs of these animals, as is known to be the case in human beings for interactions of Plasmodium vivax-Duffy antigen. ELISA tests showed that the antibody that was raised against Duffy antigens detected the presence of Duffy antigen in both subspecies and that the amount of this antigen on those erythrocyte membranes was similar. These results indicate that the greater resistance of B. taurus indicus to babesiosis cannot be explained by the absence or lower expression of Duffy antigen on RBC surfaces.

show abstract

Mechanisms of genetically-based resistance to malaria

Cited by 134 publications

References 163 publications

Population genetics of malaria resistance in humans

Population genetics of malaria resistance in humans

Glucose‐6‐phosphate metabolism in Plasmodium falciparum

Detection and quantification of Duffy antigen on bovine red blood cell membranes using a polyclonal antibody

Contact Info

Product

Resources

About