{
  "abstract": "Carbapenem-resistant Gram-negative bacteria (CRGNB) pose a severe global health threat. Carbapenem-resistant Acinetobacter baumannii (CRAB) is one of the most critical threats among CRGNB, and effective non-antibiotic therapeutic strategies are urgently needed. Bactericidal/permeability-increasing protein (BPI)-derived molecules display antibacterial and endotoxin-neutralizing activities against Gram-negative bacteria, whereas CXCL8(3-72) K11R/G31P (G31P), an analog of CXCL8 with the mutations of CXCL8 at K11 and G31 positions, could antagonize ELR-CXC chemokine-mediated neutrophil chemotaxis. Here, we engineered a dual-function fusion protein, G31P-BPI₂₃₃, to combine BPI-mediated antibacterial activity with modulation of neutrophil-driven inflammation. Recombinant G31P-BPI₂₃₃ was expressed in CHO-K1 cells and characterized through safety evaluation, endotoxin neutralization, bactericidal, serum killing, neutrophil killing, chemotaxis, cytokine, phagocytosis, and NET-associated marker assays, followed by validation in mouse models of CRAB septicemia and pneumonia. Short-term safety assessment suggested preliminary tolerability over 24 h, while G31P-BPI₂₃₃ reduced residual endotoxin activity and exhibited concentration-dependent bactericidal activity against multiple Gram-negative bacteria. At molar-matched doses, it retained G31P-mediated inhibition of neutrophil migration and BPI₂₃₃-associated bactericidal and cytokine-suppressive activities. In CRAB models, G31P-BPI₂₃₃ improved septicemia survival and reduced pneumonia-associated bacterial burden and inflammatory injury, with endpoint-specific advantages over G31P, BPI₂₃₃, or their equimolar mixture. Several pneumonia outcomes did not differ significantly between G31P-BPI₂₃₃ and colistin. Mechanistic studies using BPI-deficient mice further demonstrated that endogenous BPI contributes to bacterial clearance, endotoxin control, and neutrophil maturation and effector function during CRAB infection. Collectively, these findings identify G31P-BPI₂₃₃ as a promising host-directed antibacterial fusion protein for severe CRAB infection, with potential translational implications for the broader management of CRGNB.",
  "abstract_shown": true,
  "affiliations": [
    "China-Japan Friendship Hospital (Institute of Clinical Medical Sciences), Chinese Academy of Medical Sciences & Peking Union Medical College.",
    "National Center for Respiratory Medicine, Beijing, People's Republic of China.",
    "State Key Laboratory of Respiratory Health and Multimorbidity, Beijing, People's Republic of China.",
    "National Clinical Research Center for Respiratory Diseases, Beijing, People's Republic of China.",
    "New Cornerstone Science Laboratory, Beijing, People's Republic of China.",
    "Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing, People's Republic of China.",
    "Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, People's Republic of China.",
    "Anjun Genetech Co., Ltd, Beijing, People's Republic of China.",
    "Changping Laboratory, Chinese Academy of Medical Sciences & Peking Union Medical College."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0,
        1,
        2,
        3,
        4,
        5,
        6
      ],
      "name": "Danni Pu"
    },
    {
      "affs": [
        7
      ],
      "name": "Wei Cao"
    },
    {
      "affs": [
        7
      ],
      "name": "Jindong Chen"
    },
    {
      "affs": [
        1,
        2,
        3,
        4,
        5,
        6,
        8
      ],
      "name": "Rongrong Song"
    },
    {
      "affs": [
        1,
        2,
        3,
        4,
        5,
        6
      ],
      "name": "Jiankang Zhao"
    },
    {
      "affs": [
        0,
        1,
        2,
        3,
        4,
        5,
        6,
        8
      ],
      "name": "Bin Cao"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/dv8hzs3rydn0h.bib",
  "cited_by": 0,
  "doi": "10.1080/22221751.2026.2741787",
  "fulltext_url": "https://europepmc.org/articles/PMC13674666",
  "id": "dv8hzs3rydn0h",
  "issns": [
    "2222-1751"
  ],
  "landing_url": "https://europepmc.org/article/MED/42876256",
  "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",
      "2404|Antimicrobial Peptides and Activities"
    ]
  ],
  "openalex": "W7222028897",
  "pdf_url": "https://europepmc.org/articles/PMC13674666?pdf=render",
  "pmcid": "PMC13674666",
  "pmid": "42876256",
  "published": "2026-10-15",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/dv8hzs3rydn0h.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:46Z",
      "native_id": "MED:42876256",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42876256"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2404|Antimicrobial Peptides and Activities",
      "subfield": "microbiology"
    }
  ],
  "title": "A novel CXCL8(3-72) K11R/G31P-BPI₂₃₃ hybrid protein modulates neutrophil-driven inflammation and protects against carbapenem-resistant Acinetobacter baumannii infection.",
  "title_text": "A novel CXCL8(3-72) K11R/G31P-BPI₂₃₃ hybrid protein modulates neutrophil-driven inflammation and protects against carbapenem-resistant Acinetobacter baumannii infection.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:18:46Z",
  "url": "https://research.draconitic.com/paper/dv8hzs3rydn0h",
  "venue": "Emerging microbes & infections",
  "versions": []
}