Resurrection of the ancestral RH5 invasion ligand provides a molecular explanation for the origin of P. falciparum malaria in humans

by Francis Galaway, Ryan Yu, Anastasia Constantinou, Franck Prugnolle, Gavin J. Wright Many important infectious diseases are the result of zoonoses, in which pathogens that normally infect animals acquire mutations that enable the breaching of species barriers to permit the infection of humans. Our understanding of the molecular events that enable host switching are often limited, and yet this is a fundamentally important question.Plasmodium falciparum, the etiological agent of severe human malaria, evolved following a zoonotic transfer of parasites from gorillas. One gene —rh5—which encodes an essential ligand for the invasion of host erythrocytes, is suspected to have played a critical role in this host switch. Genome comparisons revealed an introgressed sequence in the ancestor ofP.falciparum containingrh5, which likely allowed the ancestral parasites to infect both gorilla and human erythrocytes. To test this hypothesis, we resurrected the ancestral introgressed reticulocyte-binding protein homologue 5 (RH5) sequence and used quantitative protein interaction assays to demonstrate that this ancestral protein could bind the basigin receptor from both humans and gorillas. We also showed that this promiscuous receptor binding phenotype of RH5 was shared with the parasite clade that transferred its genome segment to the ancestor ofP.falciparum, while the other lineages exhibit host-specific receptor binding, confirming the central importance of this introgression...
Source: PLoS Biology: Archived Table of Contents - Category: Biology Authors: Source Type: research

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In this study we analyze the distribution of apicomplexans across a range of both host-associated and free-living environments. Using publicly available small subunit (SSU) rRNA gene databases, high-throughput environmental sequencing (HTES) surveys, and our own generated HTES data, we developed an apicomplexan reference database, which includes the largest apicomplexan SSU rRNA tree available to date and encompasses comprehensive sampling of this group and their closest relatives. This tree allowed us to identify and correct incongruences in the molecular identification of apicomplexan sequences. Analyzing the diversity a...
Source: Frontiers in Microbiology - Category: Microbiology Source Type: research
Genetic characterisation of the erythrocyte-binding protein (PkβII) of Plasmodium knowlesi isolates from Malaysia. J Genet. 2019 Sep;98: Authors: Fong MY, Lau YL, Jelip J, Ooi CH, Cheong FW Abstract Plasmodium knowlesi contributes to the majority of human malaria incidences in Malaysia. Its uncontrollable passage among the natural monkey hosts can potentially lead to zoonotic outbreaks. The merozoite of this parasite invades host erythrocytes through interaction between its erythrocyte-binding proteins (EBPs) and their respective receptor on the erythrocytes. The regionII of P. knowlesi EBP, P. k...
Source: Journal of Genetics - Category: Genetics & Stem Cells Authors: Tags: J Genet Source Type: research
Parasites from the genus Plasmodium, the aetiological agent of malaria in humans, can also infect non-human primates (NHP), increasing the potential risk of zoonotic transmission with its associated global public...
Source: Malaria Journal - Category: Infectious Diseases Authors: Tags: Research Source Type: research
We report distinct clades of P. knowlesi that predominantly contained sequences from either human or macaque hosts for paralogous A-type and S-type 18S gene loci. We report significant partitioning of sequence distances between host species across both types of loci, and confirmed that sequences of the same locus type showed significantly biased assortment into different clades depending on their host species. Our results support the zoonotic potential of Plasmodium knowlesi, but also suggest that humans may be preferentially infected with certain strains of this parasite. Broadly, such patterns could arise through prefere...
Source: Infection, Genetics and Evolution - Category: Genetics & Stem Cells Authors: Tags: Infect Genet Evol Source Type: research
Wow - we received so many excellent comments on how parasites and the number 5 go together! Here are many of them - in no particular order - for your viewing pleasure:Pentatrichomonas hominis is a nonpathogenic intestinal flagellate named for its 5 flagella (penta from the Greek pente, meaning five + trich, pertaining to hair [flagella]). By Neil Anderson and Bernardino Rocha.There are 5 lobes of the lung, and all can be infected by Paragonimusspecies. By Brian Duresko.The are 5Plasmodiumspecies that are responsible for the bulk of malaria in humans:P. falciparum, P. vivax, P. ovale, P. malariae, andP. knowlesi(t...
Source: Creepy Dreadful Wonderful Parasites - Category: Parasitology Source Type: blogs
This study provides a preliminary snapshot of the structure of these populations, that was insufficient to answer our aim. Thus, collection of parasites from their various hosts and over time, associated with a systematic analysis of a set of genetical loci is strongly advocated in order to obtain a clear picture of the parasite population and the flow between different hosts. This is important to devise measures that will minimise the risk of transmission to humans, because zoonotic malaria impedes malaria elimination. PMID: 30999059 [PubMed - as supplied by publisher]
Source: Infection, Genetics and Evolution - Category: Genetics & Stem Cells Authors: Tags: Infect Genet Evol Source Type: research
Publication date: Available online 11 October 2018Source: Safety and Health at WorkAuthor(s): Gregory JN. Koh, Pg K. Ismail, David KohAbstractSimian malaria is a zoonotic disease caused by Plasmodium knowlesi infection. The common natural reservoir of the parasite is the macaque monkey and the vector is the Anopheles mosquito. Human cases of P. knowlesi infection has been reported in all South East Asian countries in the last decade, and it is currently the most common type of malaria seen in Malaysia and Brunei. Between 2007–2017, 73 cases of P. knowlesi infection were notified and confirmed to the Ministry of Healt...
Source: Safety and Health at Work - Category: Occupational Health Source Type: research
Plasmodium knowlesi is a zoonotic malaria parasite normally residing in long-tailed and pig-tailed macaques (Macaca fascicularis and Macaca nemestrina, respectively) found throughout Southeast Asia. Recently, kno...
Source: Malaria Journal - Category: Infectious Diseases Authors: Tags: Review Source Type: research
Abstract With the rise of global migration, international trade, and global environmental challenges such as climate change, it is not surprising that the interactions between humans and other animals are shifting. Salient infectious diseases, such as malaria and HIV (which have high burdens of disease), attract sophisticated public health frameworks and funding from global/regional organisations, such as the WHO. This unfortunately detracts attention from the many emerging zoonoses that fall under the radar as neglected tropical diseases (NTDs). This review considers the available literature and the attribution o...
Source: Topics in HIV Medicine - Category: Infectious Diseases Authors: Tags: Trop Med Infect Dis Source Type: research
AbstractDefining the linkages between landscape change, disease ecology and human health is essential to explain and predict the emergence ofPlasmodium knowlesi malaria, a zoonotic parasite residing in Southeast Asian macaques, and transmitted by species ofAnopheles mosquitos. Changing patterns of land use throughout Southeast Asia, particularly deforestation, are suggested to be the primary drivers behind the recent spread of this zoonotic parasite in humans. Local ecological changes at the landscape scale appear to be increasing the risk of disease in humans by altering the dynamics of transmission between the parasite a...
Source: EcoHealth - Category: Environmental Health Source Type: research
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