The Response of Human Skin Commensal Bacteria as a Reflection of UV Radiation: UV-B Decreases Porphyrin Production

Abstract

Recent global radiation fears reflect the urgent need for a new modality that can simply determine if people are in a radiation risk of developing cancer and other illnesses. Ultraviolet (UV) radiation has been thought to be the major risk factor for most skin cancers. Although various biomarkers derived from the responses of human cells have been revealed, detection of these biomarkers is cumbersome, probably requires taking live human tissues, and varies significantly depending on human immune status. Here we hypothesize that the reaction of Propionibacterium acnes (P. acnes), a human resident skin commensal, to UV radiation can serve as early surrogate markers for radiation risk because the bacteria are immediately responsive to radiation. In addition, the bacteria can be readily accessible and exposed to the same field of radiation as human body. To test our hypothesis, P. acnes was exposed to UV-B radiation. The production of porphyrins in P. acnes was significantly reduced with increasing doses of UV-B. The porphyrin reduction can be detected in both P. acnes and human skin bacterial isolates. Exposure of UV-B to P. acnes- inoculated mice led to a significant decrease in porphyrin production in a single colony of P. acnes and simultaneously induced the formation of cyclobutane pyrimidine dimers (CPD) in the epidermal layers of mouse skin. Mass spectrometric analysis via a linear trap quadrupole (LTQ)-Orbitrap XL showed that five peptides including an internal peptide (THLPTGIVVSCQNER) of a peptide chain release factor 2 (RF2) were oxidized by UV-B. Seven peptides including three internal peptides of 60 kDa chaperonin 1 were de-oxidized by UV-B. When compared to UV-B, gamma radiation also decreased the porphyrin production of P. acnes in a dose-dependent manner, but induced a different signature of protein oxidation/de-oxidation. We highlight that uncovering response of skin microbiome to radiation will facilitate the development of pre-symptomatic diagnosis of radiation risk in a battlefield exposure, nuclear accidents, terrorist attacks, or cancer imaging/therapy.

Porphyrin Metabolisms in Human Skin Commensal Propionibacterium acnes Bacteria: Potential Application to Monitor Human Radiation Risk

“…Currently, it is not fully clear whether there is any correlation between P. acnes strains and their distribution in the human body. Results from our laboratory have revealed that exposure of P. acnes to ultraviolet (UV) decreased the production of porphyrins in the human facial bacteria containing different strains of P. acnes and other skin bacteria [26]. Besides P. acnes , other skin resident bacteria (e.g.…”

“…Consequently, there is a linear relationship between the decrease in the height of the Soret band and the increase of X-irradiation dose [33]. Results in our recent publication have demonstrated that the production of porphyrins in P. acnes was significantly reduced with increasing doses of gamma radiation and UV-B [26]. The porphyrin reduction was detectable in both P. acnes and human skin bacterial isolates.…”

“…These intrinsic fluorophores include the amino acids tryptophan and tyrosine, and the coenzymes NADH, NADPH, and flavins [49]. Our recent results have illustrated that an internal peptide of a Lsr2 family protein (Q6AB31) was oxidized in gamma irradiated P. acnes [26]. The oxidized peptide of a Lsr2 family protein can potentially be developed as a biomarker for acute radiation sickness during nuclear accidents.…”

“…Our recent results showed that both gamma radiation and UV-B caused a reduction in the production of porphyrins although they generated distinguishable signatures of protein oxidation/de-oxidation of P. acnes [26]. Thus, establishment of a radiation-specific porphyrin profile reflecting differential porphyrin metabolites (absorption spectra) may be needed when P. acnes response is used as a radiation biomarker.…”

“…However, monitoring the porphyrin profile by quantification of the transcript levels of P. acnes -specific-enzymes (ALA synthase, and PBG deaminase) involved in porphyrin biosynthesis may circumvent the interference of skin cell prophyrins. In addition, a method developed in our laboratory by quantification of the prophyrin amounts in single colonies, not bacterial population of P. acnes [26], may eliminate the skin cell prophyrins and minimize the effect of variations in bacterial numbers on porphyrin production.…”