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Mycobacterium ulcerans mycolactone interferes with adhesion, migration and proliferation of primary human keratinocytes and HaCaT cell line

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Abstract

The pathogenicity of Mycobacterium ulcerans (Buruli ulcer) is closely associated with the secretion of exotoxin mycolactone. The cytotoxicity of mycolactone has been linked to its apoptogenic activity. We explored if low mycolactone concentrations, which are not able to induce apoptosis, can influence other essential activities on two primary human keratinocyte populations, keratinocyte stem cells (KSC) and transit amplifying cells (TAC), and on a human keratinocyte line, HaCaT. We demonstrated that 0.01 and 0.1 ng/ml mycolactone A/B are not able to induce apoptosis in primary human keratinocytes, but interfere with KSC wound repair. Moreover, the same toxin concentrations reduce cell proliferation of KSC and TAC and their ability to adhere to type IV collagen. HaCaT cells are more resistant to the toxin; nevertheless, they show a delayed woud repair when treated with 1 and 10 ng/ml mycolactone A/B. Moreover, these sub-apoptotic concentrations affect their ability to proliferate and adhere to collagen IV. Wound healing is a complex mechanism, which occurs “in vivo” as the outcome of many co-ordinated events. Sub-apoptotic mycolactone concentrations can affect essential mechanisms, which are required to achieve wound repair, such as adhesion, migration and proliferation of human keratinocytes.

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Acknowledgements

We are grateful to Prof. Pamela Small (University of Tennessee, Knoxville) for providing natural mycolactone and to Prof. Enrico Colombo (Director of Dermatologic Clinic, Novara, Italy) for clinical support.

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Authors and Affiliations

  1. Department of Translational Medicine, University of Piemonte Orientale “A. Avogadro”, Via Solaroli 17, 28100, Novara, Italy

    Francesca Graziola, Elena Colombo, Giorgio Leigheb & Chiarella Bozzo

  2. Dermatologic Department, “Maggiore della Carità” Hospital, Corso Mazzini 18, 28100, Novara, Italy

    Rossana Tiberio

Authors
  1. Francesca Graziola
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  2. Elena Colombo
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  3. Rossana Tiberio
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  4. Giorgio Leigheb
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  5. Chiarella Bozzo
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Correspondence to Chiarella Bozzo.

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The authors declare that they have no conflict of interest.

Funding

This work was partly supported by grant from University of Piemonte Orientale “A. Avogadro” to C.B.

Ethical approval

Skin specimens were collected from donors with their informed consent after the approval by ethical committee of the institute.

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Graziola, F., Colombo, E., Tiberio, R. et al. Mycobacterium ulcerans mycolactone interferes with adhesion, migration and proliferation of primary human keratinocytes and HaCaT cell line. Arch Dermatol Res 309, 179–189 (2017). https://doi.org/10.1007/s00403-017-1719-2

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  • DOI: https://doi.org/10.1007/s00403-017-1719-2

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