Biology subjects

Kuroshchenkova, A.

Publications and source records attributed to Kuroshchenkova, A..

3 recordsLinked to original sources

bioRxiv2026

A combinatorial genetics approach reveals limits to redundancy within Plasmodium falciparum invasion ligand families

To maintain infection in the human bloodstream, Plasmodium falciparum parasites undergo repeated cycles of invasion of and multiplication inside red blood cells (RBCs). Two protein families, the Erythrocyte binding-like (EBA) and Reticulocyte binding-like (Rh) proteins, are known to play a key role in invasion, mediating early stages of attachment of the P. falciparum merozoite to the host RBC. There is a degree of redundancy within these families, such that disrupting the function of individual EBA/Rh proteins in vitro is not sufficient to prevent invasion. By employing a novel approach to disrupt multiple EBA and Rh genes in combination, we systematically assessed functional interdependency across these families for the first time. This analysis, and further characterisation of mutant parasites, revealed that disruption of some pairs of EBA/Rh ligands significantly impacted P. falciparum invasion, whereas others did not. Disruption of PfEBA175 in combination with either PfRh2b or PfRh4 significantly reduced parasite multiplication in vitro, indicating that the remaining EBA/Rh proteins could not fully compensate for the absence of these three key invasion ligands. PfEBA175, PfRh2b and PfRh4 may therefore represent a critical nexus of the parasite invasion machinery, and combinatorial approaches that target these specific ligands could be a beneficial therapeutic approach.

microbiology↗

bioRxiv2025

The spatial proteome of the Plasmodium falciparum schizont illuminates the composition and evolutionary trajectories of its organelles

Malaria is caused by apicomplexan parasites of the genus Plasmodium, with all malaria symptoms and pathology caused by parasite stages that develop within, or transit between, host erythrocytes. The ability of Plasmodium cells to parasitise erythrocytes depends on distinctive intracellular compartments associated with invasion, as well as the development of unique cellular niches within the infected host cell. However, our understanding of the biology of the malaria parasite is limited by the fact that a large proportion of the parasites proteome has no known cellular location or function. To address this problem, we have generated comprehensive high-resolution maps of protein subcellular localisation for the invasive stage of the erythrocytic life cycle of Plasmodium falciparum, the major cause of malaria mortality. Using the spatial proteomics technique hyperplexed Localisation of Organelle Proteins by Isotopic Tagging (hyperLOPIT) we generated data for 3000 P. falciparum proteins expressed in late schizont stages. Our hyperLOPIT data resolved 24 distinct cellular niches, and using supervised machine-learning we can classify 1646 proteins into one of these compartments including exported sites within the host cell. Through comparative genomic analyses our data resolve the spatial patterns of cell evolution that have shaped the development of Plasmodium species and ongoing adaptive pressures and responses that challenge our efforts to manage these major disease-causing organisms.

microbiology↗

bioRxiv2023

Gut microbiome remains stable following COVID-19 vaccination in healthy and immuno-compromised individuals

The bidirectional interaction between the immune system and the gut microbiota is a key contributor to various host physiological functions. Immune-associated diseases such as cancer and autoimmunity, as well as the efficacy of immunomodulatory therapies, have been linked to microbiome variation. While COVID-19 infection has been shown to cause microbial dysbiosis, it remains understudied whether the inflammatory response associated with vaccination also impacts the microbiota. Here, we investigate the temporal impact of COVID-19 vaccination on the gut microbiome in healthy and immuno-compromised individuals; the latter included patients with primary immunodeficiency and cancer patients on immunomodulating therapies. We find that the gut microbiome remained remarkably stable post-vaccination irrespective of diverse immune status, vaccine response, and microbial composition spanned by the cohort. The stability is evident at all evaluated levels including diversity, phylum, species, and functional capacity. Our results indicate the resilience of the gut microbiome to host immune changes triggered by COVID-19 vaccination and suggest minimal, if any, impact on microbiome-mediated processes. These findings encourage vaccine acceptance, particularly when contrasted with the significant microbiome shifts observed during COVID-19 infection.

microbiology↗