{
  "abstract": "Introduction: Routine whole-genome sequencing (WGS) interpretation of Mycobacterium tuberculosis resistance focuses mainly on consensus-level mutations. Minority variants, quantified by allele frequency (AF), may indicate resistant subpopulations under drug pressure, but their association with treatment response in rifampicin-resistant or multidrug-resistant tuberculosis (RR/MDR-TB) remains unclear.\n\nMethods: We retrospectively analysed RR/MDR-TB patients treated in Ningbo, China, from 2021 to 2025, integrating clinical, phenotypic, treatment, microbiological, and WGS data. Minority resistance-associated variants (RAVs) were defined as low-frequency variants matching WHO V2 mutation catalogue entries at AF ≥ 3%, with AF ≥ 5% defining the primary higher-frequency subset. Per-drug analyses excluded patients whose target genes had median depth <200×. Associations with microbiological response were assessed using covariate-adjusted logistic regression, with higher-frequency and treatment-matched variants examined secondarily.\n\nResults: We analysed 229 RR/MDR-TB patients with linked WGS, treatment, and microbiological follow-up data. Fixed RAVs (WHO V2 catalogue-annotated) were carried by 220/229 patients (median 3, IQR 2–5). Minority RAVs at AF ≥ 3% were detected in 13 patients. Overall minority-RAV burden was not clearly associated with microbiological response after adjustment. The clearest signal involved treatment-matched AF ≥ 5% minority RAVs, whose carriers had a higher 6-month culture-positivity rate than non-carriers (4/7 [57.1%] vs 40/198 [20.2%]; adjusted odds ratio [aOR] 7.21, 95% CI 1.38–43.68; p = 0.020; q = 0.034), with a modest AUC increase from 0.675 to 0.695. Six-month positivity was highest among patients with both high fixed RAV burden and treatment-matched AF ≥ 5% minority RAVs (4/5 [80.0%] vs 15/106 [14.2%] in the low-burden non-carrier reference; Fisher’s exact p = 0.003).\n\nConclusion: Minority variants showed limited overall prognostic value, but higher-frequency treatment-matched variants provided a coherent signal for 6-month culture positivity when considered with fixed RAV burden. These exploratory findings support a cautious, treatment-aware review of selected minority variants and require external validation before clinical use.",
  "abstract_shown": true,
  "affiliations": [
    "Departments of Pulmonary Medicine, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, China",
    "Cosmos Wisdom Biotech Co. Ltd, Hangzhou, Zhejiang, China",
    "Research and Innovation Center, Cosmos Wisdom Biotech Co. Ltd, Hangzhou, Zhejiang, China",
    "Institute of Tuberculosis Prevention and Control, Ningbo Municipal Center for Disease Control and Prevention, Ningbo, Zhejiang, China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Qing Fang"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Xiangchen Li"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Yewei Lu"
    },
    {
      "affs": [
        3
      ],
      "name": "Dongliang Zhang"
    },
    {
      "affs": [
        1
      ],
      "name": "Fang Li"
    },
    {
      "affs": [
        1
      ],
      "name": "Junli Gao"
    },
    {
      "affs": [
        3
      ],
      "name": "Yang Che"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/04qf9nsb0h1e2.bib",
  "cited_by": 0,
  "doi": "10.3389/fcimb.2026.1930268",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13735570/",
  "id": "04qf9nsb0h1e2",
  "issns": [
    "2235-2988"
  ],
  "landing_url": "https://doi.org/10.3389/fcimb.2026.1930268",
  "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",
      "Original Research"
    ],
    [
      "openalex",
      "2725|Tuberculosis Research and Epidemiology"
    ]
  ],
  "openalex": "W7223184372",
  "pdf_url": "https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2026.1930268/pdf",
  "pmcid": "PMC13735570",
  "pmid": "42990861",
  "published": "2026-10-22",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/04qf9nsb0h1e2.ris",
  "sources": [
    {
      "first_seen": "2026-11-09T12:21:13Z",
      "native_id": "PMC13735570",
      "source": "pmc",
      "url": "https://doi.org/10.3389/fcimb.2026.1930268"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2725|Tuberculosis Research and Epidemiology",
      "subfield": "infectious-disease"
    }
  ],
  "title": "Resistance-gene minority variation and delayed microbiological response in rifampicin-resistant tuberculosis",
  "title_text": "Resistance-gene minority variation and delayed microbiological response in rifampicin-resistant tuberculosis",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T12:21:13Z",
  "url": "https://research.draconitic.com/paper/04qf9nsb0h1e2",
  "venue": "Frontiers in Cellular and Infection Microbiology",
  "versions": []
}