{
  "abstract": "Biofilms formed by multidrug-resistant (MDR) Pseudomonas aeruginosa and Acinetobacter baumannii are a major cause of chronic nosocomial infections and therapeutic failure. L-form antimicrobial peptides (AMPs) are rapidly degraded by proteases, whereas D-enantiomeric peptides offer enhanced resistance to proteases. Here, we synthesized L- and D-β-casein 197, a milk-derived AMP, and systematically compared their antibiofilm activities against eight clinical isolates of P. aeruginosa and A. baumannii. The D-form reduced biofilm biomass by up to 83% during formation and by up to 88% in preformed biofilms. Mechanistic analyses revealed that the D-form caused more extensive membrane disruption, as demonstrated by flow cytometry and transmission electron microscopy. Isothermal titration calorimetry showed that the D-form bound LPS with higher affinity (KD 0.8 μM vs 3.1 μM), and molecular docking identified additional hydrogen bonds with lipid A. The D-form also more effectively inhibited bacterial motility. Both peptides exhibited low cytotoxicity toward cells (>90% viability at 100 μM), and the D-form reduced bacteria-induced cytotoxicity and bacterial internalization in infected macrophages more effectively than the L-form. In a Galleria mellonella infection model, D-β-casein 197 significantly improved survival against P. aeruginosa no. R1 and A. baumannii no. 13 challenge over 96 h compared to the L-form and untreated infected controls, while larval survival remained comparable to PBS controls, indicating negligible host toxicity. These findings identify D-β-casein 197 as a potent antibiofilm peptide against MDR Gram-negative biofilms, with enhanced activity, and LPS-neutralization assays confirmed that its antimicrobial potency is, at least in part, attributable to its stronger LPS binding affinity.",
  "abstract_shown": true,
  "affiliations": [
    "Shaanxi Institute for Pediatric Diseases, Xi’an Children’s Hospital, Affiliated Children’s Hospital of Xi’an Jiaotong University, Xi’an, China",
    "Department of Clinical Laboratory, Xi’an Children’s Hospital, Affiliated Children’s Hospital of Xi’an Jiaotong University, Xi’an, China",
    "School of Electrical and Information Engineering, Jiangsu University of Technology, Changzhou, China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Kaichong Jiang"
    },
    {
      "affs": [
        1
      ],
      "name": "Wei Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Hong Lei"
    },
    {
      "affs": [
        0
      ],
      "name": "Tianhao Wang"
    },
    {
      "affs": [
        2
      ],
      "name": "Lei Xu"
    },
    {
      "affs": [
        0
      ],
      "name": "Ying Yang"
    },
    {
      "affs": [
        0
      ],
      "name": "Rui Zhou"
    },
    {
      "affs": [
        0
      ],
      "name": "Tianwei Lin"
    },
    {
      "affs": [
        0
      ],
      "name": "Yinong Huang",
      "orcid": "0009-0003-1728-6594"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/2gyvq2f9md9dx.bib",
  "cited_by": 0,
  "doi": "10.1080/21505594.2026.2749928",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13711990/",
  "id": "2gyvq2f9md9dx",
  "issns": [
    "2150-5594",
    "2150-5608"
  ],
  "landing_url": "https://doi.org/10.1080/21505594.2026.2749928",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Bacterial Pathogenesis"
    ],
    [
      "heading",
      "Research Article"
    ],
    [
      "openalex",
      "1312|Bacterial biofilms and quorum sensing"
    ]
  ],
  "openalex": "W7223187178",
  "pdf_url": "https://www.tandfonline.com/doi/pdf/10.1080/21505594.2026.2749928?needAccess=true",
  "pmcid": "PMC13711990",
  "pmid": "42908345",
  "published": "2026-10-22",
  "publisher": "Taylor & Francis",
  "ris": "https://research.draconitic.com/paper/2gyvq2f9md9dx.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T12:22:40Z",
      "native_id": "PMC13711990",
      "source": "pmc",
      "url": "https://doi.org/10.1080/21505594.2026.2749928"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Bacterial biofilms and quorum sensing",
      "subfield": "molecular-biology"
    }
  ],
  "title": "D-enantiomeric β-casein 197 disrupts biofilm-associated infection of MDR Pseudomonas aeruginosa and Acinetobacter baumannii through superior LPS binding and host cell protection",
  "title_text": "D-enantiomeric β-casein 197 disrupts biofilm-associated infection of MDR Pseudomonas aeruginosa and Acinetobacter baumannii through superior LPS binding and host cell protection",
  "type": "peer-reviewed",
  "updated_at": "2026-10-31T12:22:40Z",
  "url": "https://research.draconitic.com/paper/2gyvq2f9md9dx",
  "venue": "Virulence",
  "versions": []
}