Common skin bacteria protect their host from oxidative stress through secreted antioxidant RoxP

Tilde Andersson,Katarina Lundqvist,Anders Jensen,Gizem Ertürk Bergdahl,Helga Magnúsdóttir,Christian Brix Folsted Andersen,Kristian Stødkilde,Karim Saleh,Rolf Lood,Holger Brüggemann

doi:10.1038/s41598-019-40471-3

Tilde Andersson, Katarina Lundqvist + Show 8 more

Open Access

https://doi.org/10.1038/s41598-019-40471-3

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Abstract

Cutibacterium acnes is an abundant skin commensal with several proposed mutualistic functions. A protein with strong antioxidant activity was recently identified from the C. acnes secretome. This protein, termed RoxP, facilitated aerobic bacterial growth in vitro and ex vivo. As reducing events naturally occurred outside of the bacterial cell, it was further hypothesized that RoxP could also serve to modulate redox status of human skin. The biological function of RoxP was here assessed in vitro and in vivo, through oxidatively stressed cell cultures and through protein quantification from skin affected by oxidative disease (actinic keratosis and basal cell carcinoma), respectively. 16S rDNA amplicon deep sequencing and single locus sequence typing was used to correlate bacterial prevalence to cutaneous RoxP abundances. We show that RoxP positively influence the viability of monocytes and keratinocytes exposed to oxidative stress, and that a congruent concentration decline of RoxP can be observed in skin affected by oxidative disease. Basal cell carcinoma was moreover associated with microbial dysbiosis, characterized by reduced C. acnes prevalence. C. acnes’s secretion of RoxP, an exogenous but naturally occurring antioxidant on human skin, is likely to positively influence the human host. Results furthermore attest to its prospective usability as a biopharmaceutical.

Highlights

The age-old relationship between bacteria and the human body is vital but ambiguous
RoxP proved imperative for efficient bacterial growth in aerobic settings in vitro, as well as for the colonization of human skin ex vivo, raising the question as to whether it might have a corresponding role in vivo
C. acnes isolates identified as phylotype I displayed significantly higher expression levels of roxP compared to most phylotype II strains (Fig. 1)

Summary

Introduction

The age-old relationship between bacteria and the human body is vital but ambiguous. While most bacteria can be labelled either harmful or beneficial to our health, certain multifaceted species appear to be both[1]. Despite being a well-established opportunistic pathogen, there is a link between the autoimmune disorder psoriasis and low C. acnes prevalence[9,10] indicating that its presence is associated with mutualistic interactions[11] Consistent with this line of reasoning, we were recently able to characterize a protein, unique to C. acnes, with a suggested role in maintaining skin redox homeostasis[12]. Perhaps to a bigger extent than any other organ, our skin is subjected to high quantities of reactive oxygen species (ROS) derived from ordinary metabolic reactions, cosmetics and a continuous exposure to UV irradiation from the sun These are notorious carcinogens and have lately generated a mounting public interest in relation to antioxidant-rich food. RoxP proved imperative for efficient bacterial growth in aerobic settings in vitro, as well as for the colonization of human skin ex vivo, raising the question as to whether it might have a corresponding role in vivo

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