{
  "abstract": "Streptococcus pyogenes remains clinically susceptible to {beta}-lactam antibiotics, its first-line treatment. Yet recent reports from the US, Iceland, and Japan have identified isolates with PBP2x (a primary {beta}-lactam target) substitutions that reduced antibiotic susceptibility. To determine whether these PBP2x substitutions occurred in S. pyogenes from England and Wales, we re-analysed 2,970 invasive genomes from 2001 to 2015. We found 42 PBP2x sequence mutants in 34% (996/2,970) of the genomes, revealing an unexpected diversity in this antibiotic target. Nine emm12 isolates carried a novel double substitution, PBP2x G600A_P601H, that co-occurred with macrolide resistance genes. Experimentally, these isolates showed 2- to 4-fold elevated minimum inhibitory concentrations for four {beta}-lactam antibiotics, alongside erythromycin resistance. Other PBP2x substitutions, found across seven emm types without reduced antibiotic susceptibility, appeared driven by emm lineage expansion rather than antibiotic pressure. These findings establish a baseline for pbp2x variation, reinforcing the case for sustained genomic surveillance globally.",
  "abstract_shown": true,
  "affiliations": [
    "Imperial College London"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 11,
  "authors": [
    {
      "name": "G. Sveikauskaite"
    },
    {
      "name": "A. L. Marshall"
    },
    {
      "name": "S. Gorshkova"
    },
    {
      "name": "R. L. Guy"
    },
    {
      "name": "Y. Wan"
    },
    {
      "name": "A. Vieira"
    },
    {
      "name": "J. Coelho"
    },
    {
      "name": "K. Moganeradj"
    },
    {
      "name": "S. Sriskandan"
    },
    {
      "name": "E. Jauneikaite"
    },
    {
      "affs": [
        0
      ],
      "name": "V. W. Soo"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/dn09nz33nmex3.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.21.752073",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.21.752073v1.full",
  "id": "dn09nz33nmex3",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.21.752073v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "microbiology"
    ],
    [
      "openalex",
      "2739|Streptococcal Infections and Treatments"
    ]
  ],
  "openalex": "W7213984319",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.21.752073v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-21",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/dn09nz33nmex3.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:23:35Z",
      "native_id": "10.64898/2026.09.21.752073",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.21.752073v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:microbiology",
      "subfield": "microbiology"
    }
  ],
  "title": "Diversity of penicillin-binding protein 2x in Streptococcus pyogenes from England and Wales, 2001 to 2015",
  "title_text": "Diversity of penicillin-binding protein 2x in Streptococcus pyogenes from England and Wales, 2001 to 2015",
  "type": "preprint",
  "updated_at": "2026-10-30T12:23:35Z",
  "url": "https://research.draconitic.com/paper/dn09nz33nmex3",
  "venue": "bioRxiv",
  "versions": []
}