{
  "abstract": "Malaria parasites must undergo complex developmental transitions to complete their life cycle and transmit between vertebrate and mosquito hosts. These transitions are tightly regulated by protein phosphorylation events, yet the specific kinases involved remain poorly characterized. Here, we investigate the role of a previously uncharacterized tyrosine kinase-like protein, TKL3, in the rodent malaria parasite Plasmodium berghei. We show that TKL3 is expressed in blood stages, schizonts, gametocytes, zygotes, and ookinetes and localizes to the cytoplasm. Targeted disruption of the TKL3 gene impairs asexual blood-stage growth, male gamete fertility, and consequently compromises ookinete development. Although oocyst numbers are significantly reduced in mosquitoes, the sporozoites that do form are morphologically normal, retain hepatocyte infectivity, and complete liver-stage development. However, TKL3 knockout sporozoites showed delayed blood-stage patency due to reduced asexual replication. These findings identify TKL3 as an important regulator of parasite growth and transmission, providing new insights into kinases involved in the Plasmodium life cycle. Author summary: Malaria transmission remains a major obstacle to eradication, particularly in settings where vector control and treatment coverage are limited. Transmission-blocking interventions (TBIs) that disrupt parasite development within the mosquito vector offer a promising complementary strategy, yet few molecular targets have been validated across multiple transmission stages. Here, we identify the Plasmodium berghei kinase TKL3 as a critical regulator of parasite transmission, required for male gamete fertility, ookinete differentiation, and successful establishment of midgut infection. TKL3 knockout parasites exhibit severe defects across multiple stages, resulting in a substantial reduction in transmission. Our findings establish TKL3 as a key kinase regulating blood-stage fitness and mosquito-stage development, and provide new insights into the molecular mechanisms underlying malaria parasite transmission.",
  "abstract_shown": true,
  "affiliations": [
    "Division of Molecular Microbiology and Immunology, CSIR-Central Drug Research Institute, Lucknow, India",
    "Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India"
  ],
  "article_type": "Research Article",
  "arxiv": null,
  "author_total": 3,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Himadri Shukla"
    },
    {
      "affs": [
        1
      ],
      "name": "Nirdosh"
    },
    {
      "name": "Satish Mishra"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/9bd4zz6ndn213.bib",
  "cited_by": 0,
  "doi": "10.1371/journal.ppat.1014582",
  "fulltext_url": "https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014582",
  "id": "9bd4zz6ndn213",
  "issns": [
    "1553-7374"
  ],
  "landing_url": "https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014582",
  "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": [
    [
      "openalex",
      "2739|Malaria Research and Control"
    ],
    [
      "plos",
      "/Biology and life sciences/Biochemistry/Enzymology/Enzymes/Protein kinases"
    ],
    [
      "plos",
      "/Biology and life sciences/Biochemistry/Proteins/Enzymes/Protein kinases"
    ],
    [
      "plos",
      "/Biology and life sciences/Cell biology/Cellular types/Animal cells/Germ cells/Gametocytes"
    ],
    [
      "plos",
      "/Biology and life sciences/Cell biology/Cellular types/Animal cells/Germ cells/Ova/Zygotes"
    ],
    [
      "plos",
      "/Biology and life sciences/Developmental biology/Life cycles/Parasitic life cycles"
    ],
    [
      "plos",
      "/Biology and life sciences/Parasitology/Parasite groups/Apicomplexa/Oocysts"
    ],
    [
      "plos",
      "/Biology and life sciences/Parasitology/Parasite groups/Apicomplexa/Plasmodium"
    ],
    [
      "plos",
      "/Biology and life sciences/Parasitology/Parasite groups/Apicomplexa/Sporozoites"
    ],
    [
      "plos",
      "/Biology and life sciences/Parasitology/Parasitic life cycles"
    ],
    [
      "plos",
      "/Medicine and health sciences/Medical conditions/Parasitic diseases"
    ]
  ],
  "openalex": "W7211925567",
  "pdf_url": "https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1014582&type=printable",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-08",
  "publisher": "Public Library of Science",
  "ris": "https://research.draconitic.com/paper/9bd4zz6ndn213.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:56Z",
      "native_id": "10.1371/journal.ppat.1014582",
      "source": "plos",
      "url": "https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014582"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "plos:cell biology",
      "subfield": "cell-biology"
    },
    {
      "field": "biology",
      "origin": "plos:parasitology",
      "subfield": "microbiology"
    }
  ],
  "title": "TKL3 regulates blood-stage fitness, male gamete fertility, and transmission-stage development in Plasmodium berghei",
  "title_text": "TKL3 regulates blood-stage fitness, male gamete fertility, and transmission-stage development in Plasmodium berghei",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:56Z",
  "url": "https://research.draconitic.com/paper/9bd4zz6ndn213",
  "venue": "PLOS Pathogens",
  "versions": []
}