New Discovery Unravels Malaria Invasion Mechanism
Medical science just took a step forward in the continuing arms race between it and creationism's divine malevolence to try to prevent its parasite, Plasmodium falciparum from killing 600,000 people, mostly children, a year, mostly in Africa.
Creationists who use the traditional excuse that it's not their god who designs parasites but another intelligent designer - Sin - should refresh their memories of Michael J Beh's 'proof' that their god exists by falsely claiming that anti-malarial drug resistance in P. falciparum must have been intelligently designed because the (wrong) mathematical model he used gave the infinitesimally small probability it was intelligently designed to give, so could not have evolved.
So, they can't have it both ways: if evidence of design in parasites, no matter how spurious, is evidence for their god then their god is responsible for the design of those parasites. If not, then Michael J Behe's carefully concocted 'proof' is nothing of the sort.
The alternative is the blasphemous claim that there is another supernatural deity with powers to create living things, over whom their god has no power or authority.
So, while creationists are struggling with trying to hold two mutually exclusive views simultaneously, biomedical scientists are trying to unravel the devilishly clever way this parasite overcomes our defences to do what creationists must believe it was designed to do - make us sick and increase the suffering in the world.
This is the latest breakthrough medical science has just announced.
It was made by researchers from by the Swiss Tropical and Public Health Institute (Swiss TPH) and Griffith University’s Institute for Glycomics, led by Professor Gerd Pluschke of Swiss TPH. Their discovery concerns the way the parasite gains access to the red blood cells to begin their destruction. It is published, open access, in Cell Reports and is explained in a Swiss PTH news release:
A recent breakthrough sheds light on how the malaria parasite, Plasmodium falciparum, invades human red blood cells. The study, led by the Swiss Tropical and Public Health Institute (Swiss TPH) and Griffith University’s Institute for Glycomics, reveals the role of a sugar called sialic acid in this invasion process. The findings, published yesterday in Cell Reports, have major implications for malaria vaccine and drug development.The team's paper in Cell Reports gives technical details and background:
With 249 million cases of malaria and 608,000 deaths in 2022, malaria has remained an intractable global health threat. The malaria parasite Plasmodium falciparum is the leading cause of severe malaria and is responsible for the largest portion of malaria deaths. All clinical symptoms of malaria are caused by the multiplication of malaria parasites in the red blood cells.
Key component found for malaria invasion
P. falciparum is known to invade human red blood cells, but the precise details of the targets that the parasite binds to has not been known to date. Although we know that the malaria protein, cystein-rich protective antigen (CyRPA), is essential for the invasion of red blood cells, its precise role in this process was not understood. A multidisciplinary, collaborative research team from six institutions, led by investigators at Swiss TPH in Switzerland and Institute for Glycomics in Australia examined the binding properties of CyPRA. The researchers discovered that a sugar called sialic acid is a key component of the red blood cell surface that is recognized by the malaria parasite, and which is essential for the invasion process. The findings were published in the peer-reviewed journal Cell Reports.Malaria parasite adapted to humansWe are now demonstrating that P. falciparum CyRPA binds to a specific carbohydrate structure (glycan) present on the red blood cell surface. The CyRPA protein is highly adapted to bind to a glycan terminating with a sialic acid. The discovery of the key function of CyRPA in host cell invasion provides an explanation for the parasite inhibitory activity of CyRPA-specific antibodies.
Professor Gerd Pluschke, co-corresponding author
Group Leader of Molecular Immunology
Swiss TPH, Allschwil, Switzerland.
Implications for vaccine and drug developmentHumans differ from other primates because they can only produce one type of sialic acid, called Neu5Ac. This genetic difference between humans and closely related primates has long been proposed to contribute to the species-specific targeting of malaria parasites. In this study, we show that the human form of sialic acid, Neu5Ac, is strongly preferred by the human-specific malaria parasite P. falciparum, and may explain the adaptation of this parasite to humans.
Michael Jennings, co-corresponding author
Acting Director
Institute for Glycomics
Griffith University, Gold Coast, QLD, Australia.
Vaccines targeting the P. falciparum pre-erythrocytic stages are registered for use. However, they only show moderate levels of efficacy. There is no registered vaccine against the blood stage of malaria, but there is intensive research on blood stage vaccines.
Moreover, as the emergence of drug resistance in the parasites that cause malaria is a major health threat, the study’s findings offer hope for new antimalarial drugs that are urgently needed.The discovery of the key function of CyRPA in host cell invasion strongly supports the concept to clinically test CyRPA as a blood stage vaccine target.
Professor Gerd Pluschke.
The essential binding activity of CyRPA to a specific glycan also validates CyRPA as drug target, and we demonstrate that small molecule inhibitors that interfered with this function can inhibit malaria replication in our study.
Michael Jennings.
HighlightsIt's hard to think of a nastier parasite on humans than the malaria-causing Plasmodium falciparum yet acolytes of Michael J Behe lap up his book in which he 'proved' it was designed by their supposedly omnibenevolent god and wave his 'proof' as conclusive evidence of its existence.
- Plasmodium falciparum CyRPA binds to carbohydrates with terminal 2-6-linked Neu5Ac
- Lectin activity of Plasmodium falciparum CyRPA contributes to erythrocyte invasion
- Targeting lectin activity with drugs and antibodies is a promising anti-malarial strategy
Summary
Plasmodium falciparum is a human-adapted apicomplexan parasite that causes the most dangerous form of malaria. P. falciparum cysteine-rich protective antigen (PfCyRPA) is an invasion complex protein essential for erythrocyte invasion. The precise role of PfCyRPA in this process has not been resolved. Here, we show that PfCyRPA is a lectin targeting glycans terminating with α2-6-linked N-acetylneuraminic acid (Neu5Ac). PfCyRPA has a >50-fold binding preference for human, α2-6-linked Neu5Ac over non-human, α2-6-linked N-glycolylneuraminic acid. PfCyRPA lectin sites were predicted by molecular modeling and validated by mutagenesis studies. Transgenic parasite lines expressing endogenous PfCyRPA with single amino acid exchange mutants indicated that the lectin activity of PfCyRPA has an important role in parasite invasion. Blocking PfCyRPA lectin activity with small molecules or with lectin-site-specific monoclonal antibodies can inhibit blood-stage parasite multiplication. Therefore, targeting PfCyRPA lectin activity with drugs, immunotherapy, or a vaccine-primed immune response is a promising strategy to prevent and treat malaria.
Introduction
Invasion of human erythrocytes by Plasmodium falciparum merozoites involves a complex cascade of highly specific molecular interactions between merozoite adhesins and host receptors mediating recognition, attachment, and active entry of the parasites into erythrocytes. Prior to tight junction formation, host cell “sensing” is mediated by the P. falciparum erythrocyte binding-like (PfEBL) and reticulocyte binding protein homolog (PfRh) protein families.1 With only one exception, i.e., PfRh5,2 individual disruption of the PfRh- and PfEBL-encoding genes does not prevent invasion, reflecting functional redundancy of the early receptor-ligand interactions.3,4 Together with P. falciparum cysteine-rich protective antigen (PfCyRPA)5 and P. falciparum Rh5 interacting protein (PfRipr),6 PfRh5 is part of a ternary invasion complex,7 with all three components being refractory to genetic disruption and therefore essential.2,6,8 Antibodies specific for each of the three components efficiently block parasite growth in both in vitro and in vivo models5,6,9,10,11,12; however, the mechanism by which invasion-blocking, anti-PfCyRPA antibodies act is uncertain.13Day, Christopher J.; Favuzza, Paola; Bielfeld, Sabrina; Haselhorst, Thomas; Seefeldt, Leonie; Hauser, Julia; Shewell, Lucy K.; Flueck, Christian; Poole, Jessica; Jen, Freda E.-C.; Schäfer, Anja; Dangy, Jean-Pierre; Gilberger, Tim-W.; França, Camila Tenorio;; Duraisingh, Manoj T.; Tamborrini, Marco; Brancucci, Nicolas M.B.; Grüring, Christof; Filarsky, Michael; Jennings, Michael P.; Pluschke, Gerd
The essential malaria protein PfCyRPA targets glycans to invade erythrocytes Cell Reports (2024) 43(4). 10.1016/j.celrep.2024.114012
Copyright: © 2024 The authors.
Published by Cell Press. Open access.
Reprinted under a Creative Commons Attribution 4.0 International license (CC BY 4.0)
One can only wonder at the mindset of those who imagine P. falciparum is a subject for admiration, not of a mindless evolutionary process, but as the special creation of an all-loving god.
The Malevolent Designer: Why Nature's God is Not Good
Illustrated by Catherine Webber-Hounslow.
The Unintelligent Designer: Refuting The Intelligent Design Hoax
There's no way an all good, all loving, omnibenevolent creator God would have created malaria. And it wasn't Adam and Eve that's to blame. Malaria and the mosquitoes are older than Humanity. Mosquitoes have been tormenting and killing animals millions of years before humans first appeared.
ReplyDeleteHow delusional is Michael J. Behe? By crediting God for creating the malaria parasite, he is unintentionally crediting God for creating Natural evil and the suffering and death it causes. Why would anyone want to believe this? Why would anyone call this an all good being? It's self evident it couldn't be. It's not even close to being all good. It doesn't seem to bother Michael J. Behe that His God is the creator and source of evil, suffering, and death. This is the kind of mentality which describes creationists and Fundamentalists. These people worship an evil deity and don't realize it, and they call this evil being Omnibenevolent and All good, loving, merciful, perfect, all mighty, all wise. This shows how delusional and how out of touch with reality these religious people are. This kind of mentality is unrealistic and childishly delusional.
I ask Michael J. Behe this question. "Are you proud of a being, creator, deity, or God who creates malaria and countless other Natural evils?" Is this something admirable? This is to me a huge embarrassment and does not deserve any praise whatsoever. This isn't something to be proud of at all. This is something to be ashamed of. But it seems this creator has no shame for the evil, suffering, and loss of life He created, caused, and allows, and has no heart, no morals, and no conscience. This being has no regard for the well being, safety, and happiness of its creation and has no regard for life itself. Amoral, non moral, indifferent, mentally blind, morally blind, heartless, pitiless, merciless, and immeasurably, unimaginably cruel.
It's also a mystery that after millions of years of suffering, death, and extinctions from both Nature and from human beings, this deity/creator/ God continues to allow the cruelties. Why is this being unable or unwilling to go back and fix and heal the defects, flaws, and horrors in His creation? Why is this creator incapable of healing its flawed, screwed up creation?Is it too lazy, or too stupid, or just doesn't care? Does it desire to have evil, sin, suffering, and death in its creation? Why then call it all good?j Or maybe it's insane? Maybe this creator is just not right in the head. I would also point out that this being, whether it's called a creator or deity or God, is extremely remote, aloof, disconnected, disinterested, disengaged, dissociated, distorted and withdrawn and hidden from His creation. Why? If as we're told that God wants to have a personal close loving relationship with every person then why does He hide from us? Why does He choose to remain silent, hidden, withdrawn, and absent. We have a God who behaves as if He doesn't exist. An absentee landlord. Even some of the clergy in churches are admitting they don't feel God's presence but feel His absence.
Malaria is one of the worst scourge. It's easier to believe that the Devil or a demon created this horrible disease. A loving God would never do such a thing. Malaria is just one of the countless reasons why the world is the hellhole that it is. Let's hope that scientists can discover better ways to rid the world of malaria and rid the world of other diseases.