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New insights into the role of Cutibacterium acnes-derived extracellular vesicles in inflammatory skin disorders

View ORCID ProfileMaria Pol Cros, View ORCID ProfileJúlia Mir-Pedrol, Lorena Toloza, View ORCID ProfileNastassia Knödlseder, View ORCID ProfileMarc Güell, Julien Maruotti, Christos C. Zouboulis, View ORCID ProfileMaria-José Fábrega Fernández
doi: https://doi.org/10.1101/2022.12.15.520547
Maria Pol Cros
1Department of Medicine and Life Sciences, Universitat Pompeu Fabra, Barcelona, ES
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Júlia Mir-Pedrol
1Department of Medicine and Life Sciences, Universitat Pompeu Fabra, Barcelona, ES
2Universitaet Tuebingen Fachbibliothek Mathematik und Physik Tubingen, Baden-Württemberg, DE
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Lorena Toloza
1Department of Medicine and Life Sciences, Universitat Pompeu Fabra, Barcelona, ES
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Nastassia Knödlseder
1Department of Medicine and Life Sciences, Universitat Pompeu Fabra, Barcelona, ES
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Marc Güell
1Department of Medicine and Life Sciences, Universitat Pompeu Fabra, Barcelona, ES
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Julien Maruotti
3Phenocell, Grasse, FR
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Christos C. Zouboulis
4Hochschulklinik für Dermatologie, Venerologie und Allergologie, Immunologisches Zentrum. Städtisches Klinikum Dessau. Medizinische Hochschule Brandenburg Theodor Fontane und Fakaltät für Gesundheitswissenschaften Brandenburg. Auenweg
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Maria-José Fábrega Fernández
1Department of Medicine and Life Sciences, Universitat Pompeu Fabra, Barcelona, ES
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  • ORCID record for Maria-José Fábrega Fernández
  • For correspondence: maria-jose.fabrega@upf.edu
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ABSTRACT

Background Cutibacterium acnes (C. acnes) is one of the most prevalent bacteria that form the human skin microbiota and, depending on multifactorial conditions it can help to maintain the skin homeostasis. Actually, different phylotypes of C. acnes have been associated with different degrees of acne vulgaris development, while others, such as the H1 subtype, have been detected in patients with non-acneic skin. However, due to the physiology of the skin, the skin microbiota neither has direct access to the skin’s sebaceous glands nor to the main immune cells, as they are protected by a sebum layer. Therefore, the inter-kingdom communication relies on secreted factors and bacterial extracellular vesicles (EVs). In this context, the purpose of this project was to study the role of EVs secreted by three different phylotypes of C. acnes (A1 as pathogenic, H1 as beneficial and H2 as commensal).

Results Main findings showed that the proteomic profile of the cargo embodied in the EVs reflects unique characteristics of the different C. acnes phylotypes in terms of lifestyle, survival and virulence. Moreover, in vitro skin models showed an extended pro-inflammatory modulation of A1 EVs, while H1 EVs displayed a high sebum-reducing potential.

Conclusions This study has highlighted the role of C. acnes EVs as key modulators during skin alterations, specially H1 EVs as an alternative based-natural treatment to fight acne vulgaris symptomatology.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • We made a mistake and overlooked the fact that we had an agreement No. SZ95-A 213-1 with Dr. Zouboulis who provided us the human immortalized sebaceous gland cell line SZ95 and in exchange he has to be co-author of this publication. Therefore, we added him in the author list and we did small changes in the manuscript based on his new recommendations.

  • https://bitbucket.org/synbiolab/fabrega_vesicles/src/master/

  • ABBREVIATIONS

    C. acnes
    Cutibacterium acnes
    EVs
    extracellular vesicles
    PBS
    phosphate-buffered saline
    SN
    supernatant
    TEM
    transmission electron microscopy
    NTA
    nanoparticle tracking analysis
    SDS-PAGE
    sodium dodecyl sulfate-polyacrylamide gel electrophoresis
    PBS
    phosphate-buffered saline
    CPS
    cycles per second
    DDA
    data-dependent acquisition
    AGC
    auto gain control
    HCD
    high-energy collision dissociation
    FDR
    false discovery rate
    XIC
    extracted ion current
    ATCC
    American Type Culture Collection
    DMEM
    Dulbecco’s Modified Eagle Medium
    FBS
    Fetal Bovine Serum
    EGFr
    recombinant human epidermal growth factor
    CaCl2
    calcium chloride
    RPMI
    Roswell Park Memorial Institute medium
    RT
    room temperature
    WGA
    wheat germ agglutinin
    RT-qPCR
    quantitative real time-PCR analysis
    PCi-SEB
    human iPSC-derived sebocytes
    AA5
    5 μM of arachidonic acid
    SD
    standard deviation
    GO
    Gene Ontology
    IL
    interleukin
    CITE
    biofilm matrix dynamics
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    Posted January 23, 2023.
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    New insights into the role of Cutibacterium acnes-derived extracellular vesicles in inflammatory skin disorders
    Maria Pol Cros, Júlia Mir-Pedrol, Lorena Toloza, Nastassia Knödlseder, Marc Güell, Julien Maruotti, Christos C. Zouboulis, Maria-José Fábrega Fernández
    bioRxiv 2022.12.15.520547; doi: https://doi.org/10.1101/2022.12.15.520547
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    New insights into the role of Cutibacterium acnes-derived extracellular vesicles in inflammatory skin disorders
    Maria Pol Cros, Júlia Mir-Pedrol, Lorena Toloza, Nastassia Knödlseder, Marc Güell, Julien Maruotti, Christos C. Zouboulis, Maria-José Fábrega Fernández
    bioRxiv 2022.12.15.520547; doi: https://doi.org/10.1101/2022.12.15.520547

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