{
  "abstract": "Protein intrinsically disordered regions (IDRs) are characterized by their lack of defined stable tertiary structure and are capable of adopting multiple conformations for functional activity. In chaperone proteins, these flexible regions are often sites of condition specific protein-protein interactions. In Listeria monocytogenes (Lm), PrsA2 is a peptidyl prolyl isomerase (PPIase) chaperone that promotes pathogenesis through the maturation of secreted proteins including the pore forming toxin, listeriolysin O (LLO). PrsA2 is composed of a PPIase domain and foldase domain that are critical for secreted protein function. In addition, PrsA2 contains an uncharacterized unstructured region, the carboxyl-terminal tail (C-tail) consisting of 10-amino acid residues rich in serine. Here, we demonstrate that the PrsA2 C-tail and its serine residues are critical for Lm bacterial virulence in a mouse septicemic model. We trace this virulence defect to a reduction in secreted LLO activity exhibited by Lm PrsA2 C-tail bacterial mutants. Further, we use biophysical and biochemical assays to establish that the PrsA2 C-tail is required for interacting with and folding the LLO toxin. We then characterize the PrsA2 C-tail as a critical factor in Lm survival under stress conditions and highlight its crucial role against cell-wall targeting antibiotics. PrsA homologs are well-conserved in Gram-positive bacteria, and this work characterizes the Lm PrsA2 C-tail, demonstrating its contribution to bacterial virulence, chaperone function, and secreted protein activity. Author summary: Compared to eukaryotes, unstructured protein regions within bacterial proteomes are much less abundant, yet they are increasingly recognized as important for protein function and regulation. In this study, we characterize an unstructured C-terminal region of the peptidyl-prolyl isomerase chaperone PrsA2 from the Gram-positive food-borne pathogen Listeria monocytogenes (Lm). We demonstrate that this PrsA2 C-tail region is a key determinant of Lm virulence, enabling the activity of the major pore-forming toxin listeriolysin O. In addition, the PrsA2 C-tail is critical for overcoming cell-wall targeting antibiotics. Since PrsA homologs are well conserved in Gram-positive bacteria, our findings may be widely applicable to several Gram-positive pathogens.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Biological Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America",
    "Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, Illinois, United States of America"
  ],
  "article_type": "Research Article",
  "arxiv": null,
  "author_total": 4,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Allison H. Kumar"
    },
    {
      "affs": [
        1
      ],
      "name": "Charles Agbavor"
    },
    {
      "name": "Francis Alonzo 3rd"
    },
    {
      "name": "Laty A. Cahoon"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/0drebq0t3fq3d.bib",
  "cited_by": 0,
  "doi": "10.1371/journal.ppat.1014676",
  "fulltext_url": "https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014676",
  "id": "0drebq0t3fq3d",
  "issns": [
    "1553-7374"
  ],
  "landing_url": "https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014676",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|Heat shock proteins research"
    ],
    [
      "plos",
      "/Biology and life sciences/Biochemistry/Proteins/Amino acids/Hydroxyl amino acids/Serine"
    ],
    [
      "plos",
      "/Biology and life sciences/Biochemistry/Proteins/Protein interactions"
    ],
    [
      "plos",
      "/Biology and life sciences/Biochemistry/Proteins/Protein structure/Protein folding"
    ],
    [
      "plos",
      "/Biology and life sciences/Biochemistry/Proteins/Recombinant proteins"
    ],
    [
      "plos",
      "/Biology and life sciences/Cell biology/Cellular structures and organelles/Cell walls"
    ],
    [
      "plos",
      "/Biology and life sciences/Cell biology/Cellular types/Animal cells/Blood cells/White blood cells/Macrophages"
    ],
    [
      "plos",
      "/Biology and life sciences/Cell biology/Cellular types/Animal cells/Immune cells/White blood cells/Macrophages"
    ],
    [
      "plos",
      "/Biology and life sciences/Immunology/Immune cells/White blood cells/Macrophages"
    ],
    [
      "plos",
      "/Biology and life sciences/Microbiology/Bacteriology/Gram positive bacteria"
    ],
    [
      "plos",
      "/Biology and life sciences/Molecular biology/Macromolecular structure analysis/Protein structure/Protein folding"
    ],
    [
      "plos",
      "/Medicine and health sciences/Immunology/Immune cells/White blood cells/Macrophages"
    ],
    [
      "plos",
      "/Medicine and health sciences/Pathology and laboratory medicine/Pathogens/Virulence factors"
    ],
    [
      "plos",
      "/Physical sciences/Chemistry/Chemical compounds/Organic compounds/Amino acids/Hydroxyl amino acids/Serine"
    ],
    [
      "plos",
      "/Physical sciences/Chemistry/Organic chemistry/Organic compounds/Amino acids/Hydroxyl amino acids/Serine"
    ]
  ],
  "openalex": "W7220476932",
  "pdf_url": "https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1014676&type=printable",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-05",
  "publisher": "Public Library of Science",
  "ris": "https://research.draconitic.com/paper/0drebq0t3fq3d.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:37Z",
      "native_id": "10.1371/journal.ppat.1014676",
      "source": "plos",
      "url": "https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014676"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "plos:cell biology",
      "subfield": "cell-biology"
    },
    {
      "field": "biology",
      "origin": "plos:immunology",
      "subfield": "immunology"
    }
  ],
  "title": "The serine-rich C-terminal tail of the Listeria monocytogenes secretion chaperone PrsA2 is critical for bacterial virulence and resistance to cell-wall active antibiotics",
  "title_text": "The serine-rich C-terminal tail of the Listeria monocytogenes secretion chaperone PrsA2 is critical for bacterial virulence and resistance to cell-wall active antibiotics",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:37Z",
  "url": "https://research.draconitic.com/paper/0drebq0t3fq3d",
  "venue": "PLOS Pathogens",
  "versions": []
}