{
  "abstract": "Biofilm formation by Helicobacter pylori is a major driver of antibiotic tolerance and treatment failure, yet the signaling pathways that trigger biofilm development under sub-inhibitory antibiotic pressure remain poorly understood. Here, we show that sub-MIC levels of metronidazole, amoxicillin, and ciprofloxacin potently induce dense H. pylori biofilms. Through transcriptomic and genetic analyses, we identify the two-component system CrdRS as a central signaling hub that orchestrates this response via the bidirectional regulation of two ATP-binding cassette (ABC) transporters. Phosphorylated CrdR binds to AC-rich promoter motifs to directly activate plpA, which encodes a substrate-binding protein that drives exopolysaccharide secretion and matrix assembly. Concomitantly, CrdR represses glnP, which encodes an inner-membrane permease, thereby relieving transcriptional inhibition of the L-asparaginase gene ansB. This derepression triggers aberrant reactive oxygen species (ROS) accumulation, which promotes oxidative stress-dependent biofilm maturation. Through phenotypic analysis of crdRS deletion mutants, phosphorylation-defective point mutants (CrdRD53A and CrdSH173A), and exogenous hydrogen peroxide (H₂O₂) induction, we demonstrate that CrdRS is required for mediating antibiotic-induced stress responses in a manner genetically separable from ROS sensing. Collectively, our findings establish a dual-mechanism model in which CrdRS orchestrates antibiotic-induced biofilm formation by simultaneously controlling matrix production and intracellular ROS generation. Notably, glnP expression was significantly lower in clinical multidrug-resistant isolates than in drug-sensitive ones, whereas plpA showed the opposite trend. These findings provide a mechanistic foundation for developing CrdRS-targeted strategies to combat biofilm-associated H. pylori infections.",
  "abstract_shown": true,
  "affiliations": [
    "Key Laboratory for Experimental Teratology of the Ministry of Education and Department of Microbiology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China",
    "Department of Pathology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 12,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Wenxin Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Lu Zhang"
    },
    {
      "affs": [
        1
      ],
      "name": "Yanlin Sun"
    },
    {
      "affs": [
        0
      ],
      "name": "Mingzhong Zhao"
    },
    {
      "affs": [
        0
      ],
      "name": "Shujing Xu"
    },
    {
      "affs": [
        0
      ],
      "name": "Han Yu"
    },
    {
      "affs": [
        0
      ],
      "name": "Wenjing Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Jinmeng Liu"
    },
    {
      "affs": [
        0
      ],
      "name": "Wenyue Ma"
    },
    {
      "affs": [
        0
      ],
      "name": "Xiaoyu Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Ziyan Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Yundong Sun",
      "orcid": "0000-0001-5260-2212"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/4fys15evnee0c.bib",
  "cited_by": 0,
  "doi": "10.1128/aac.00882-26",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13731178/",
  "id": "4fys15evnee0c",
  "issns": [
    "0066-4804",
    "1098-6596"
  ],
  "landing_url": "https://doi.org/10.1128/aac.00882-26",
  "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",
      "Mechanisms of Action: Physiological Effects"
    ],
    [
      "openalex",
      "1312|Bacterial biofilms and quorum sensing"
    ]
  ],
  "openalex": "W7220362017",
  "pdf_url": null,
  "pmcid": "PMC13731178",
  "pmid": "42831884",
  "published": "2026-10-05",
  "publisher": "American Society for Microbiology (ASM)",
  "ris": "https://research.draconitic.com/paper/4fys15evnee0c.ris",
  "sources": [
    {
      "first_seen": "2026-11-08T12:21:25Z",
      "native_id": "PMC13731178",
      "source": "pmc",
      "url": "https://doi.org/10.1128/aac.00882-26"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Bacterial biofilms and quorum sensing",
      "subfield": "molecular-biology"
    }
  ],
  "title": "The two-component system CrdRS mediates sub-inhibitory antibiotic-induced biofilm formation in Helicobacter pylori via bidirectional regulation of transporters PlpA and GlnP",
  "title_text": "The two-component system CrdRS mediates sub-inhibitory antibiotic-induced biofilm formation in Helicobacter pylori via bidirectional regulation of transporters PlpA and GlnP",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T12:21:25Z",
  "url": "https://research.draconitic.com/paper/4fys15evnee0c",
  "venue": "Antimicrobial Agents and Chemotherapy",
  "versions": []
}