{
  "abstract": "Nutrient sensing and utilization are critical for microbes to adapt to their environment and evade predators. The encapsuled yeast Cryptococcus neoformans has a unique ability to sense and utilize the sugar inositol as both a signaling molecule and as a carbon source. This trait is advantageous not only in the natural environment but also to promote its pathogenesis, including invasion of the central nervous system. In this study, we have identified a novel inositol transporter-like receptor (transceptor) Itr4 that coordinates inositol and glucose metabolism by regulating inositol transporters (ITRs) and glucose sensor Hxs1. Itr4 binds inositol and regulates the function of other ITRs and its loss leads to a significant decrease in inositol uptake activity, resulting in a lack of mating, reduced capsule size, reduced blood–brain barrier (BBB) penetration, and virulence attenuation. Mutagenesis analysis of Itr4 protein identified an essential N-terminal tail and two amino acids, Q388 and Q389, as sites of functional importance. The ITR4Q388A, Q389A allele showed a dominant phenotype with increased inositol uptake, enlarged capsule and significantly attenuated virulence. In summary, we identify a new C. neoformans inositol transceptor, Itr4, the first such example in eukaryotes, with novel regulatory roles in both inositol and glucose metabolism and fungal virulence.\n\nHow pathogens prioritize nutrients while adapting to changing environments is central to their survival and ability to cause disease. This study shows that the inositol-sensing receptor Itr4 enables Cryptococcus neoformans to maintain inositol use even when glucose is abundant, linking nutrient sensing to carbon metabolism and virulence.",
  "abstract_shown": true,
  "affiliations": [
    "Public Health Research Institute, New Jersey Medical School, Rutgers University, Newark, New Jersey, United States of America.",
    "Department of Microbiology, Biochemistry and Molecular Genetics, New Jersey Medical School, Rutgers University, Newark, New Jersey, United States of America.",
    "Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Medicine, Baltimore, Maryland, United States of America.",
    "Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, Arizona, United States of America.",
    "Department of Medicinal Chemistry, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, New Jersey, United States of America.",
    "School of Biological Sciences, Nanyang Technological University, Singapore, Singapore.",
    "Department of Biomedical Sciences and Pathobiology, College of Veterinary Medicine, Virginia Tech, Blacksburg, Virginia, United States of America."
  ],
  "article_type": "Research Article",
  "arxiv": null,
  "author_total": 11,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Yina Wang"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Robert J Tancer"
    },
    {
      "affs": [
        2
      ],
      "name": "Maggie Wear"
    },
    {
      "affs": [
        3
      ],
      "name": "Katrina M Jackson"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Yu Zhang"
    },
    {
      "affs": [
        4
      ],
      "name": "Kan Li",
      "orcid": "0000-0002-0825-1934"
    },
    {
      "affs": [
        4
      ],
      "name": "Jun Wang",
      "orcid": "0000-0002-4845-4621"
    },
    {
      "affs": [
        5
      ],
      "name": "Yong-Gui Gao"
    },
    {
      "affs": [
        6
      ],
      "name": "Kirsten Nielsen"
    },
    {
      "affs": [
        2
      ],
      "name": "Arturo Casadevall"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Chaoyang Xue",
      "orcid": "0000-0001-8196-1468"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/1hee9bxtbfwp2.bib",
  "cited_by": 0,
  "doi": "10.1371/journal.pbio.3003709",
  "fulltext_url": "https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3003709",
  "id": "1hee9bxtbfwp2",
  "issns": [
    "1545-7885",
    "1544-9173"
  ],
  "landing_url": "https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3003709",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2713|Fungal Infections and Studies"
    ],
    [
      "plos",
      "/Biology and life sciences/Genetics/Fungal genetics"
    ],
    [
      "plos",
      "/Biology and life sciences/Genetics/Gene expression"
    ],
    [
      "plos",
      "/Biology and life sciences/Microbiology/Medical microbiology/Microbial pathogens/Fungal pathogens"
    ],
    [
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      "/Biology and life sciences/Mycology/Fungal genetics"
    ],
    [
      "plos",
      "/Biology and life sciences/Mycology/Fungal pathogens"
    ],
    [
      "plos",
      "/Biology and life sciences/Organisms/Eukaryota/Fungi/Cryptococcus"
    ],
    [
      "plos",
      "/Biology and life sciences/Organisms/Eukaryota/Fungi/Yeast"
    ],
    [
      "plos",
      "/Biology and life sciences/Organisms/Eukaryota/Fungi/Yeast/Saccharomyces/Saccharomyces cerevisiae"
    ],
    [
      "plos",
      "/Medicine and health sciences/Medical conditions/Infectious diseases/Fungal diseases/Yeast infections"
    ],
    [
      "plos",
      "/Medicine and health sciences/Pathology and laboratory medicine/Pathogens/Microbial pathogens/Fungal pathogens"
    ],
    [
      "plos",
      "/Physical sciences/Chemistry/Chemical compounds/Organic compounds/Carbohydrates/Monosaccharides/Glucose"
    ],
    [
      "plos",
      "/Physical sciences/Chemistry/Organic chemistry/Organic compounds/Carbohydrates/Monosaccharides/Glucose"
    ],
    [
      "plos",
      "/Research and analysis methods/Animal studies/Experimental organism systems/Model organisms/Saccharomyces cerevisiae"
    ],
    [
      "plos",
      "/Research and analysis methods/Animal studies/Experimental organism systems/Yeast and fungal models/Saccharomyces cerevisiae"
    ],
    [
      "plos",
      "/Research and analysis methods/Model organisms/Saccharomyces cerevisiae"
    ]
  ],
  "openalex": "W7221593224",
  "pdf_url": "https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.3003709&type=printable",
  "pmcid": "PMC13686456",
  "pmid": "42868157",
  "published": "2026-10-13",
  "publisher": "Public Library of Science",
  "ris": "https://research.draconitic.com/paper/1hee9bxtbfwp2.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:30Z",
      "native_id": "10.1371/journal.pbio.3003709",
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      "url": "https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3003709"
    },
    {
      "first_seen": "2026-10-30T12:19:00Z",
      "native_id": "MED:42868157",
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  "subjects": [
    {
      "field": "biology",
      "origin": "plos:microbiology",
      "subfield": "microbiology"
    }
  ],
  "title": "An inositol receptor Itr4 coordinates carbon catabolite regulation and virulence in Cryptococcus neoformans",
  "title_text": "An inositol receptor Itr4 coordinates carbon catabolite regulation and virulence in Cryptococcus neoformans",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:00Z",
  "url": "https://research.draconitic.com/paper/1hee9bxtbfwp2",
  "venue": "PLOS Biology",
  "versions": []
}