Exploring effects of bacterial colonisation in an all-human skin model

Griffiths, Katie Jane (2024) Exploring effects of bacterial colonisation in an all-human skin model. Doctoral thesis, University of East Anglia.

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Abstract

The skin is the barrier between the body and the environment, with a resident microbiome hosting a reservoir of microorganisms which may promote or impede skin health and wound healing. Staphylococcus epidermidis is an opportunistic pathogen resident on healthy human skin. Its dual nature, both promoting skin barrier health through competition with other bacteria and also causing/exacerbating infections, make it an ideal study organism when characterising the skin host response.

With growing antimicrobial resistance, topical antiseptics are often the first line of defence against infection, however the bulk of antiseptic studies investigate how well a product can kill bacteria, but not the effect it can have on the host.

An ex vivo full thickness human skin explant model was optimised to better support bacterial survival, and the skin host response was characterised through candidate and unbiased approaches at both the gene- and protein-level. Notably, S. epidermidis induced antimicrobial peptide (AMP) and inflammatory cytokine upregulation in ex-vivo skin explants that was well-conserved across donors. Expression of these genes was upregulated in response to both bacteria and sterile inflammation (modelled by LPS and cytokine stimulation). Immunohistochemically, AMP S100A7 was found to localise to the upper epidermal layers after bacterial exposure, and culturing explants with biocides appeared to weaken this response.

Complementary 2D studies in a keratinocyte cell line and primary cell experiments noted similar trends, with AMP secretion linked to bacterial survival rates. Restoration of skin homeostasis after infection is a balance between removing pathogens whilst not impacting healthy tissue. Of the antiseptics tested, peracetic acid was the most cytotoxic in the 2D models, however it was the only antiseptic tested in the skin explant model that exhibited complete bacterial kill.

The data obtained will be useful for future antiseptic characterisation and assessment of skin host responses to clinically-relevant concentrations and timepoints.

Item Type:	Thesis (Doctoral)
Faculty \ School:	Faculty of Science > School of Biological Sciences
Depositing User:	Kitty Laine
Date Deposited:	11 Jun 2025 11:24
Last Modified:	11 Jun 2025 11:24
URI:	https://ueaeprints.uea.ac.uk/id/eprint/99455
DOI:

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