In vitro assessment of skin sensitization, irritability and toxicity of bacteriocins and reuterin for possible topical applications

Abstract

Bacteriocins and reuterin are promising antimicrobials for application in food, veterinary, and medical sectors. In the light of their high potential for application in hand sanitizer, we investigated the skin toxicity of reuterin, microcin J25, pediocin PA-1, bactofencin A, and nisin Z in vitro using neutral red and LDH release assays on NHEK cells. We determined their skin sensitization potential using the human cell line activation test (h-CLAT). Their skin irritation potential was measured on human epidermal model EpiDerm™. We showed that the viability and membrane integrity of NHEK cells remained unaltered after exposure to bacteriocins and reuterin at concentrations up to 400 µg/mL and 80 mg/mL, respectively. Furthermore, microcin J25 and reuterin showed no skin sensitization at concentrations up to 100 µg/mL and 40 mg/mL, respectively, while pediocin PA-1, bactofencin A, and nisin Z caused sensitization at concentrations higher than 100 µg/mL. Tissue viability was unaffected in presence of bacteriocins and reuterin at concentrations up to 200 µg/mL and 40 mg/mL, respectively, which was confirmed by measuring cytokine IL-1α and IL-8 levels and by histological analysis. In conclusion, the current study provides scientific evidence that some bacteriocins and reuterin, could be safely applied topically as sanitizers at recommended concentrations.

The pearl jubilee of microcin J25: thirty years of research on an exceptional lasso peptide

“…The skin toxicity and skin sensitization of reuterin and various bacteriocins, including MccJ25, were assessed on human cell lines in view of topical applications and hand sanitizers. 247 Here, it was shown how concentrations of MccJ25 up to 400 mg mL −1 and 100 mg mL −1 did not exhibit toxicity to NHEK cells or skin sensitization, respectively.…”

Application of the Reuterin System as Food Preservative or Health-Promoting Agent: A Critical Review

“…Furthermore, 3-HPA had no hemolytic effect on blood cells at 270 mM [ 51 ]. In addition, the purified 3-HPA at bactericidal concentrations of 40 mg/L did not exert any skin toxicity [ 52 ].…”

Resistance to the Bacteriocin Lcn972 Deciphered by Genome Sequencing

“…In this context, research on bacteriocins, gene-encoded antimicrobial peptides synthesized by bacteria, is shifting towards their applications in the clinical field. This shift is exemplified by the increasing number of reports on bacteriocin toxicity [ 2 , 3 , 4 ] and on their effectiveness in animal models (revised in [ 5 ]). Moreover, bacteriocins are seen not only as anti-infectives but also as potential microbiome-editing tools [ 6 ].…”