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Published on: August 5, 2021
Apical membrane antigen 1 mediates apicomplexan parasite attachment but is dispensable for host cell invasion
Daniel Y Bargieri1, Nicole Andenmatten, Vanessa Lagal
11] Institut Pasteur, Malaria Biology and Genetics Unit, Department of Parasitology and Mycology, 28 Rue du Dr Roux, Paris, France [2].
Abstract:
Apicomplexan parasites invade host cells by forming a ring-like junction with the cell surface and actively sliding through the junction inside an intracellular vacuole. Apical membrane antigen 1 is conserved in apicomplexans and a long-standing malaria vaccine candidate. It is considered to have multiple important roles during host cell penetration, primarily in structuring the junction by interacting with the rhoptry neck 2 protein and transducing the force generated by the parasite motor during internalization. Here, we generate Plasmodium sporozoites and merozoites and Toxoplasma tachyzoites lacking apical membrane antigen 1, and find that the latter two are impaired in host cell attachment but the three display normal host cell penetration through the junction. Therefore, apical membrane antigen 1, rather than an essential invasin, is a dispensable adhesin of apicomplexan zoites. These genetic data have implications on the use of apical membrane antigen 1 or the apical membrane antigen 1-rhoptry neck 2 interaction as targets of intervention strategies against malaria or other diseases caused by apicomplexans.
Insights
Apicomplexan parasites invade host cells. Apical membrane antigen 1 (AMA1) is not essential for invasion, but rather a dispensable adhesin, impacting parasite attachment strategies.
Area of Science:
- Parasitology
- Cell Biology
- Infectious Diseases
Background:
- Apicomplexan parasites invade host cells via a unique junctional mechanism.
- Apical membrane antigen 1 (AMA1) is a conserved protein in apicomplexans and a malaria vaccine candidate.
- AMA1 is thought to be crucial for host cell penetration by structuring the junction and transducing force.
Purpose of the Study:
- To investigate the essentiality of AMA1 in host cell invasion by apicomplexan parasites.
- To determine the specific role of AMA1 during the invasion process.
Main Methods:
- Generation of Plasmodium sporozoites, merozoites, and Toxoplasma tachyzoites lacking AMA1.
- Phenotypic analysis of host cell attachment and penetration in genetically modified parasites.
Main Results:
- Parasites lacking AMA1 showed impaired host cell attachment.
- Despite attachment defects, parasites lacking AMA1 exhibited normal host cell penetration.
- AMA1 is not essential for the invasion process itself.
Conclusions:
- Apical membrane antigen 1 (AMA1) functions as a dispensable adhesin, not an essential invasin, in apicomplexan zoites.
- Targeting AMA1 or its interaction with rhoptry neck 2 may not be effective for blocking parasite invasion.
- Findings impact the development of intervention strategies against apicomplexan-caused diseases like malaria.
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