Iron sourcing strategies and adaptive protein responses to iron deprivation in the intraerythrocytic parasite Babesia divergens
4 affiliations
- 1Department of Disease Vectors and Pathogens, Institute of Parasitology, Biology Centre of the Czech Academy of Sciences, České Budějovice, Czech Republic
- 2Department of Parasitology, Faculty of Science, BIOCEV, Charles University, Vestec, Czech Republic
- 3Departments of Molecular Biology and Biochemistry and Pharmaceutical Sciences, University of California, Irvine, California, United States of America
- 4Faculty of Science, University of South Bohemia, České Budějovice, Czech Republic
Abstract
Iron is indispensable for the survival and pathogenicity of Babesia parasites, yet the mechanisms underlying its acquisition remain largely unresolved. In contrast to other apicomplexan parasites, tick-borne Babesia species rapidly lose the parasitophorous vacuole following erythrocyte invasion and do not form hemozoin, suggesting the evolution of distinct strategies for iron metabolism. Here, we demonstrate that Babesia divergens utilizes a sequential, multi-route iron acquisition system to meet its metabolic demands within host erythrocytes. Kinetic uptake analyses reveal a pronounced preference for ferrous iron (Fe2+), which is imported through an active, energy-dependent process supported by extracellular ferric reductase activity that converts host-derived ferric iron (Fe3+) into a bioavailable form prior to uptake. Using immunogold transmission electron microscopy, we provide evidence for the active internalization of host transferrin and show that parasite proliferation is dose-dependently inhibited by apo-transferrin, establishing iron as a limiting factor for parasite growth. Quantitative proteomic profiling revealed a limited, stage-specific response to deferoxamine-induced iron deprivation. Three proteins showed statistically significant changes in abundance in free merozoites: the conserved multipass membrane protein Bdiv_019230 increased, whereas the hypothetical protein Bdiv_002300 and the putative serine hydroxymethyltransferase Bdiv_027330 decreased. No proteins reached the statistical significance threshold in intraerythrocytic parasites. These results identify a small set of statistically supported candidates for investigating the response of extracellular B. divergens merozoites to iron-restricted conditions. Author summary: To survive and proliferate within vertebrate hosts, the intraerythrocytic parasite Babesia divergens must obtain iron from the tightly regulated environment of red blood cells. Although iron is essential for parasite growth and survival, iron acquisition and homeostasis in Babesia remain largely unexplored. In this study, we investigated iron metabolism in B. divergens through a series of complementary approaches.
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BibTeX
@article{levytska2026iron,
title = {{Iron sourcing strategies and adaptive protein responses to iron deprivation in the intraerythrocytic parasite Babesia divergens}},
author = {Viktoriya Levytska and Jan Mach and Luise Robbertse and Celia W. Goulding and Ronald Malych and Marie Jalovecka and Robert Sutak and Daniel Sojka},
journal = {PLOS Neglected Tropical Diseases},
year = {2026},
month = nov,
doi = {10.1371/journal.pntd.0014861},
url = {https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0014861},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Iron sourcing strategies and adaptive protein responses to iron deprivation in the intraerythrocytic parasite Babesia divergens
AU - Viktoriya Levytska
AU - Jan Mach
AU - Luise Robbertse
AU - Celia W. Goulding
AU - Ronald Malych
AU - Marie Jalovecka
AU - Robert Sutak
AU - Daniel Sojka
PY - 2026
DA - 2026/11/04
JO - PLOS Neglected Tropical Diseases
DO - 10.1371/journal.pntd.0014861
UR - https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0014861
AB - Iron is indispensable for the survival and pathogenicity of Babesia parasites, yet the mechanisms underlying its acquisition remain largely unresolved. In contrast to other apicomplexan parasites, tick-borne Babesia species rapidly lose the parasitophorous vacuole following erythrocyte invasion and do not form hemozoin, suggesting the evolution of distinct strategies for iron metabolism. Here, we demonstrate that Babesia divergens utilizes a sequential, multi-route iron acquisition system to meet its metabolic demands within host erythrocytes. Kinetic uptake analyses reveal a pronounced preference for ferrous iron (Fe2+), which is imported through an active, energy-dependent process supported by extracellular ferric reductase activity that converts host-derived ferric iron (Fe3+) into a bioavailable form prior to uptake. Using immunogold transmission electron microscopy, we provide evidence for the active internalization of host transferrin and show that parasite proliferation is dose-dependently inhibited by apo-transferrin, establishing iron as a limiting factor for parasite growth. Quantitative proteomic profiling revealed a limited, stage-specific response to deferoxamine-induced iron deprivation. Three proteins showed statistically significant changes in abundance in free merozoites: the conserved multipass membrane protein Bdiv_019230 increased, whereas the hypothetical protein Bdiv_002300 and the putative serine hydroxymethyltransferase Bdiv_027330 decreased. No proteins reached the statistical significance threshold in intraerythrocytic parasites. These results identify a small set of statistically supported candidates for investigating the response of extracellular B. divergens merozoites to iron-restricted conditions. Author summary: To survive and proliferate within vertebrate hosts, the intraerythrocytic parasite Babesia divergens must obtain iron from the tightly regulated environment of red blood cells. Although iron is essential for parasite growth and survival, iron acquisition and homeostasis in Babesia remain largely unexplored. In this study, we investigated iron metabolism in B. divergens through a series of complementary approaches.
SN - 1935-2735
ER -