The inner membrane complex protein, IMC55, is dispensable for intraerythrocytic development of Plasmodium falciparum
Fig 1 Identifying the interacting partners of PfERC.
Plasmodium falciparum, an obligate intracellular Apicomplexan parasite and the causative agent of malaria, must reside and replicate within a host cell during the intraerythrocytic stage. At the end of its replicative cycle, the parasite breaks down two biological membranes using a proteolytic cascade to release invasive daughter cells known as merozoites to continue its asexual expansion. We have previously shown that PfERC is an essential regulator of the parasite egress proteolytic cascade. In this work, we expand our investigation to show that PfERC may also function in parasite invasion into the red blood cell (RBC). To determine how PfERC functions in parasite invasion, we used proteomic approaches to identify several PfERC-interacting proteins. One of the PfERC interacting partners, IMC55, localizes to a specialized double-membraned organelle called the inner membrane complex. Proteins localizing to the inner membrane complex have been shown to be required for schizont-stage segmentation, as well as merozoite motility during subsequent re-invasion. Whole-genome transposon mutagenesis screens predict that the PfERC-interactor, IMC55, is essential for the intraerythrocytic asexual cycle. To determine the biological function of IMC55, we generated conditional mutants of IMC55 using two different approaches. Our data show that IMC55 is not required for asexual replication. Following inducible expression of this gene using two conditional systems, we find there is no defect in replicative fitness during the asexual blood stage. Taken together, these data demonstrate that the function of IMC55 is either dispensable or redundant for the Plasmodium falciparum asexual blood stages.
Importance: The inner membrane complex or IMC is a set of flattened cisternal membrane compartments originating from the ancestral Alveolata lineage, where it is shared among ciliates, dinoflagellates, as well as Apicomplexans like Plasmodium and Toxoplasma. We identified a transmembrane protein known as IMC55, and using multiple conditional systems, show that it is not required for Plasmodium falciparum asexual growth. This is likely due to redundant function, or it may have a role in the mosquito stages of the parasite lifecycle.
Grace W Vick, Manuel A Fierro, Annabella Castiglione, Lenna Park, Carrie Brooks, Vasant Muralidharan. Microbiol Spectr. 2026 Jun 10:e0365625. doi: 10.1128/spectrum.03656-25.