{
  "abstract": "Antimicrobial-resistance surveillance reports an isolate as susceptible, intermediate, or resistant, and a genome as a list of resistance genes; neither shows whether a population is uniformly wild-type or harbours a resistant minority. Both discard the shape of the minimum inhibitory concentration (MIC) distribution, which encodes within-population resistance heterogeneity. We treated the Miller-Madow-corrected Shannon entropy of that distribution as a phenotypic state variable and asked whether it carries information beyond the resistance genome. Entropy was computed on a fixed 19-bin MIC ladder for 1,612 species-drug distributions (European Committee on Antimicrobial Susceptibility Testing [EUCAST], 252 species) and 11,259 species-drug-year series (Antimicrobial Testing Leadership and Surveillance [ATLAS], 241 species, 2004–2024), paired with resistance-gene annotations (Comprehensive Antibiotic Resistance Database) for 64 species (6,382 genomes). Entropy rose with the non-wild-type fraction defined by epidemiological cut-offs (Spearman ρ = 0.72), indexing coexisting subpopulations. Across 50 paired species, resistance-gene content explained less than 2% of the variance in phenotypic distributional complexity (ordinary least squares R2 = 0.014, p = 0.406). This decoupling was the most reproducible feature, recovered under phylogenetic correction (Pagel-λ phylogenetic generalised least squares p = 0.891), a mechanism-matched comparison (pooled R2 = 0.002), and a 145-specification multiverse, although only |r| ≥ 0.39 could be excluded. In 33,862 Bacterial and Viral Bioinformatics Resource Center genomes with MICs, catalogued genes explained a minority of isolate-level entropy (median 20.7%, 95% confidence interval [CI] 18.5–25.2%). Population MIC complexity is therefore not reconstructable from the genome, and the residual is descriptive but stable: 14% of species expressed more complexity than their gene content predicts, 16% less, and 70% remained aligned, including all six ESKAPE species (Enterococcus, Staphylococcus, Klebsiella, Acinetobacter, Pseudomonas, Enterobacter). Entropy was reproducible across estimators (Spearman ρ ≥ 0.92) and discriminated later resistant-subpopulation emergence in walk-forward testing (area under the curve [AUC] = 0.695, 95% CI 0.629–0.756), similar to a momentum baseline (0.665), but did not forecast escalation in a hold-out split at the record’s midpoint (AUC = 0.535, 95% CI 0.472–0.594). MIC-distribution entropy therefore resolves a phenotypic dimension of resistance, heterogeneity consistent with heteroresistance, and silent genomic reservoirs, that is invisible to breakpoint categories and gene counts.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "Original Research",
  "arxiv": null,
  "author_total": 3,
  "authors": [
    {
      "name": "Siva Bharathi Ulaganathan"
    },
    {
      "name": "C. Shreya"
    },
    {
      "name": "Karthikeyan Sivashanmugam"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/2hdap894c3myf.bib",
  "cited_by": 0,
  "doi": "10.3389/fmicb.2026.1976579",
  "fulltext_url": null,
  "id": "2hdap894c3myf",
  "issns": [
    "1664-302X"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fmicb.2026.1976579",
  "language": null,
  "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": [
    [
      "feed-journal",
      "biology/microbiology"
    ]
  ],
  "openalex": null,
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-04",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/2hdap894c3myf.ris",
  "sources": [
    {
      "first_seen": "2026-11-04T12:20:46Z",
      "native_id": "10.3389/fmicb.2026.1976579",
      "source": "feed-frontiers",
      "url": "https://www.frontiersin.org/articles/10.3389/fmicb.2026.1976579"
    },
    {
      "first_seen": "2026-11-04T12:21:25Z",
      "native_id": "10.3389/fmicb.2026.1976579",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fmicb.2026.1976579/full"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "feed-journal:biology/microbiology",
      "subfield": "microbiology"
    }
  ],
  "title": "A phenotypic state variable for antimicrobial resistance: MIC-distribution entropy exposes population heterogeneity and phenotypically quiet genomic reservoirs",
  "title_text": "A phenotypic state variable for antimicrobial resistance: MIC-distribution entropy exposes population heterogeneity and phenotypically quiet genomic reservoirs",
  "type": "peer-reviewed",
  "updated_at": "2026-11-06T00:21:17Z",
  "url": "https://research.draconitic.com/paper/2hdap894c3myf",
  "venue": "Frontiers in Microbiology",
  "versions": []
}