{
  "abstract": "ESX type VII secretion systems of Mycobacterium tuberculosis ( Mtb ) export proteins that are essential for bacterial virulence and adaptation to the host. While ESX-1, ESX-3, and ESX-5 have been extensively characterized, the physiological role of ESX-2 and its impact on host-pathogen interactions remain largely unexplored. Experimental evidence suggests that the esx-2 expression is regulated by WhiB5, a transcriptional regulator induced in in vitro nutrient-starvation conditions, and required for Mtb reactivation in the mouse infection model. This study aimed at characterizing the ESX-2 secretion system, with a focus on its role in Mtb adaptation/survival under nutrient-related stress conditions and in virulence. The analysis of the esx-2 gene expression profiles revealed an upregulation of selected esx-2 genes during Mtb cultivation in nutrient-depleted media or upon reactivation from a hypoxia-induced dormancy status. Consistently, the characterization of a panel of Mtb ESX-2 mutant strains (inactivated for selected esx-2 genes encoding ESX-2 components or deleted for the entire esx-2 locus ) demonstrated an involvement of ESX-2 in Mtb survival in nutrient starvation and in promoting Mtb growth after reactivation from dormancy. Moreover, the intracellular growth kinetics of ESX-2 mutants in ex vivo models (THP-1 and A549 cells) and their attenuation profiles in the severe combined immunodeficient mice indicated that a functional ESX-2 is required for optimal Mtb replication inside the host. Overall, these findings identify ESX-2 as a modulator of Mtb survival under selected nutrient-starvation-related stress conditions peculiar to intracellular environments, thus contributing to the intracellular and in vivo Mtb growth. IMPORTANCE ESX-2 is the second most recently evolved ESX secretion system in mycobacteria, largely conserved in Mycobacterium tuberculosis ( Mtb ) and other slow-growing pathogenic mycobacteria. Among the ESX secretion systems, ESX-2 is the least extensively characterized, and to date, its function is largely unknown. This study provides novel experimental evidence of the impact of ESX-2 on Mtb physiology and host-pathogen interaction. A functional ESX-2 is required for Mtb survival under hostile conditions, such as nutrient limitation conditions, and is involved in Mtb growth reactivation from a dormant state in vitro . Moreover, the observed role of ESX-2 in promoting Mtb replication in cellular and animal models emphasizes the impact of this secretion system in Mtb adaptation to the human host.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 12,
  "authors": [
    {
      "name": "Camilla Vullo"
    },
    {
      "name": "Mariagrazia Di Luca"
    },
    {
      "name": "Cosmeri Rizzato"
    },
    {
      "name": "Wafa Frigui"
    },
    {
      "name": "Fadel Sayes"
    },
    {
      "name": "Noemi Poma"
    },
    {
      "name": "Riccardo Farinella"
    },
    {
      "name": "Antonella Lupetti"
    },
    {
      "name": "Giovanni Signore"
    },
    {
      "name": "Arianna Tavanti"
    },
    {
      "name": "Roland Brosch"
    },
    {
      "name": "Daria Bottai"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/0qb7zabghxr04.bib",
  "cited_by": 0,
  "doi": "10.1128/spectrum.01299-26",
  "fulltext_url": null,
  "id": "0qb7zabghxr04",
  "issns": [
    "2165-0497"
  ],
  "landing_url": "https://pasteur.hal.science/pasteur-05842432v1",
  "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": [
    [
      "hal",
      "0.sdv"
    ],
    [
      "openalex",
      "2725|Tuberculosis Research and Epidemiology"
    ]
  ],
  "openalex": "W7223797792",
  "pdf_url": "https://pasteur.hal.science/pasteur-05842432/document",
  "pmcid": null,
  "pmid": "42937333",
  "published": "2026-10-27",
  "publisher": "American Society for Microbiology",
  "ris": "https://research.draconitic.com/paper/0qb7zabghxr04.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:02Z",
      "native_id": "pasteur-05842432",
      "source": "hal",
      "url": "https://pasteur.hal.science/pasteur-05842432v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2725|Tuberculosis Research and Epidemiology",
      "subfield": "infectious-disease"
    }
  ],
  "title": "The ESX-2 type VII secretion system is required for Mycobacterium tuberculosis survival under nutrient starvation and for reactivation from dormancy",
  "title_text": "The ESX-2 type VII secretion system is required for Mycobacterium tuberculosis survival under nutrient starvation and for reactivation from dormancy",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:18:02Z",
  "url": "https://research.draconitic.com/paper/0qb7zabghxr04",
  "venue": "Microbiology Spectrum",
  "versions": []
}