{
  "abstract": "Sensory induction of mecA expression plays a pivotal role in mediating broad-spectrum β-lactam resistance of MRSA. In contemporary MRSA isolates, sensory induction of β-lactam resistance originates at the membrane-associated BlaR1, which, upon detection of β-lactam drugs, triggers a signal transduction cascade that promotes mecA induction. We hereby show that phosphorylation of BlaR1, mediated through the serine-threonine kinase, Stk1, stabilizes its membrane-spanning state and retention, allowing for proper drug sensing and subsequent signal transduction events to occur, culminating in mecA-mediated β-lactam resistance. Our results demonstrate that targeting Stk1 can potentiate synthetic lethality to β-lactams in the majority of naturally isolated strains of MRSA. We additionally present the structural and kinetic basis for a Stk1-inhibitor complex that can enable rational design of Stk1-directed anti-MRSA therapeutics in the future. Our results reveal a novel role of the STK signaling pathway in bacterial protein stabilization in the cytosolic membrane.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Microbial Pathogenesis, School of Dentistry, University of Maryland, Baltimore, MD, USA.",
    "Institute of Marine and Environmental Technology (IMET), Baltimore, MD, USA.",
    "Department of Biochemistry and Molecular Biology and Centre for Blood Research, University of British Columbia, Vancouver, British Columbia, Canada.",
    "Integrated Data Sciences Section, Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.",
    "University of Maryland Greenebaum Comprehensive Cancer Center, University of Maryland, Baltimore, MD, USA.",
    "Functional Cellular Networks Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.",
    "Division of Infectious Disease, Department of Medicine, San Francisco General Hospital, San Francisco, CA, USA.",
    "Department of Microbial Pathogenesis, School of Dentistry, University of Maryland, Baltimore, MD, USA. schatterjee@umaryland.edu.",
    "Institute of Marine and Environmental Technology (IMET), Baltimore, MD, USA. schatterjee@umaryland.edu."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 16,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Raymond Poon",
      "orcid": "0009-0009-8620-8235"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Nidhi Satishkumar",
      "orcid": "0000-0003-1290-1159"
    },
    {
      "affs": [
        2
      ],
      "name": "Wesley A Mosimann",
      "orcid": "0000-0003-2580-1042"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Vedangi D Hayatnagarkar",
      "orcid": "0009-0000-0516-9321"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Swagata Bose",
      "orcid": "0000-0002-8655-7867"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Vijay Hemmadi",
      "orcid": "0000-0002-8169-6817"
    },
    {
      "affs": [
        3
      ],
      "name": "Skyler Kuhn",
      "orcid": "0000-0003-0606-2125"
    },
    {
      "affs": [
        0,
        1,
        4
      ],
      "name": "Aditi Chatterjee"
    },
    {
      "affs": [
        2
      ],
      "name": "Liam Worrall"
    },
    {
      "affs": [
        5
      ],
      "name": "Nathan P Manes",
      "orcid": "0000-0001-6701-3314"
    },
    {
      "affs": [
        2
      ],
      "name": "J Andrew N Alexander",
      "orcid": "0000-0002-8759-1389"
    },
    {
      "affs": [
        3
      ],
      "name": "Justin Lack"
    },
    {
      "affs": [
        6
      ],
      "name": "Henry F Chambers",
      "orcid": "0000-0001-5317-4491"
    },
    {
      "affs": [
        5
      ],
      "name": "Aleksandra Nita-Lazar",
      "orcid": "0000-0002-8523-605X"
    },
    {
      "affs": [
        2
      ],
      "name": "Natalie C J Strynadka"
    },
    {
      "affs": [
        7,
        8
      ],
      "name": "Som S Chatterjee",
      "orcid": "0000-0002-7138-4449"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/ekcckyeb85bk3.bib",
  "cited_by": 0,
  "doi": "10.1038/s41467-026-77668-w",
  "fulltext_url": "https://europepmc.org/articles/PMC13677706",
  "id": "ekcckyeb85bk3",
  "issns": [
    "2041-1723"
  ],
  "landing_url": "https://europepmc.org/article/MED/42894009",
  "language": "eng",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2725|Antimicrobial Resistance in Staphylococcus"
    ]
  ],
  "openalex": "W7122594336",
  "pdf_url": "https://europepmc.org/articles/PMC13677706?pdf=render",
  "pmcid": "PMC13677706",
  "pmid": "42894009",
  "published": "2026-09-16",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/ekcckyeb85bk3.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:41Z",
      "native_id": "MED:42894009",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42894009"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2725|Antimicrobial Resistance in Staphylococcus",
      "subfield": "infectious-disease"
    }
  ],
  "title": "Stk1 is required for BlaR1-mediated broad-spectrum β-lactam resistance in epidemic-causing strains of Staphylococcus aureus.",
  "title_text": "Stk1 is required for BlaR1-mediated broad-spectrum β-lactam resistance in epidemic-causing strains of Staphylococcus aureus.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:41Z",
  "url": "https://research.draconitic.com/paper/ekcckyeb85bk3",
  "venue": "Nature communications",
  "versions": []
}