{
  "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.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Disease Vectors and Pathogens, Institute of Parasitology, Biology Centre of the Czech Academy of Sciences, České Budějovice, Czech Republic",
    "Department of Parasitology, Faculty of Science, BIOCEV, Charles University, Vestec, Czech Republic",
    "Departments of Molecular Biology and Biochemistry and Pharmaceutical Sciences, University of California, Irvine, California, United States of America",
    "Faculty of Science, University of South Bohemia, České Budějovice, Czech Republic"
  ],
  "article_type": "Research Article",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Viktoriya Levytska"
    },
    {
      "affs": [
        1
      ],
      "name": "Jan Mach"
    },
    {
      "affs": [
        2
      ],
      "name": "Luise Robbertse"
    },
    {
      "affs": [
        3
      ],
      "name": "Celia W. Goulding"
    },
    {
      "name": "Ronald Malych"
    },
    {
      "name": "Marie Jalovecka"
    },
    {
      "name": "Robert Sutak"
    },
    {
      "name": "Daniel Sojka"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/7813ra7fata7t.bib",
  "cited_by": 0,
  "doi": "10.1371/journal.pntd.0014861",
  "fulltext_url": "https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0014861",
  "id": "7813ra7fata7t",
  "issns": [
    "1935-2735"
  ],
  "landing_url": "https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0014861",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "plos",
      "/Biology and life sciences/Biochemistry/Proteins/Post-translational modification/Heme"
    ],
    [
      "plos",
      "/Biology and life sciences/Cell biology/Cellular types/Animal cells/Blood cells/Red blood cells"
    ],
    [
      "plos",
      "/Biology and life sciences/Organisms/Eukaryota/Protozoans/Parasitic protozoans/Babesia"
    ],
    [
      "plos",
      "/Biology and life sciences/Parasitology/Parasite groups/Apicomplexa"
    ],
    [
      "plos",
      "/Biology and life sciences/Parasitology/Parasite groups/Apicomplexa/Babesia"
    ],
    [
      "plos",
      "/Biology and life sciences/Parasitology/Parasite groups/Apicomplexa/Merozoites"
    ],
    [
      "plos",
      "/Biology and life sciences/Parasitology/Parasite groups/Apicomplexa/Plasmodium"
    ],
    [
      "plos",
      "/Biology and life sciences/Parasitology/Quantitative parasitology/Parasitemia"
    ],
    [
      "plos",
      "/Medicine and health sciences/Medical conditions/Parasitic diseases"
    ]
  ],
  "openalex": null,
  "pdf_url": "https://journals.plos.org/plosntds/article/file?id=10.1371/journal.pntd.0014861&type=printable",
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-04",
  "publisher": "Public Library of Science",
  "ris": "https://research.draconitic.com/paper/7813ra7fata7t.ris",
  "sources": [
    {
      "first_seen": "2026-11-05T12:20:11Z",
      "native_id": "10.1371/journal.pntd.0014861",
      "source": "plos",
      "url": "https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0014861"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "plos:parasitology",
      "subfield": "microbiology"
    }
  ],
  "title": "Iron sourcing strategies and adaptive protein responses to iron deprivation in the intraerythrocytic parasite Babesia divergens",
  "title_text": "Iron sourcing strategies and adaptive protein responses to iron deprivation in the intraerythrocytic parasite Babesia divergens",
  "type": "peer-reviewed",
  "updated_at": "2026-11-06T12:20:43Z",
  "url": "https://research.draconitic.com/paper/7813ra7fata7t",
  "venue": "PLOS Neglected Tropical Diseases",
  "versions": []
}