Probiotics as Novel Anti-infective agents for skin

Abstract

Wound infection is a serious problem that may prolong the healing process and complicate management. Probiotics have been reported to be effective in inhibiting both intestinal and extra-intestinal pathogens. The topical use of probiotic- derived products may offer new prophylactic and therapeutic alternatives that are efficient and safe to use. The aim of this doctoral thesis, therefore, was to investigate the possibility of using probiotic-derived products to inhibit both the planktonic and biofilm forms of specific wound-associated pathogens. Lysates and supernatants of five candidate probiotics (Lactobacillus plantarum, Lactobacillus reuteri, Bifidobacterium longum, Escherichia coli Nissle 1917 and Lactobacillus rhamnosus GG) were investigated against planktonic and biofilm forms of five wound-associated pathogens: Staphylococcus aureus, Streptococcus pyogenes, Escherichia coli, Pseudomonas aeruginosa and Acinetobacter baumannii. Co-incubation of wound pathogens with probiotic-derived supernatants showed varying levels of inhibition. B. longum supernatant was the most inhibitory supernatant and induced significant reduction in the growth rate of S. aureus, E. coli, P. aeruginosa and A. baumannii. A significant reduction in the growth rate of S. aureus, E. coli and A. baumannii was also seen when these pathogens were co- incubated with the supernatant of both L. plantarum and L. rhamnosus GG. However, these supernatants were rendered ineffective following pH neutralisation indicating that the inhibition was predominantly due to the production of acids. A significant reduction in the growth rate of S. aureus and S. pyogenes was seen when these pathogens were co-incubated with lysates of L. plantarum and L. reuteri. The lysate of L. plantarum also significantly reduced the planktonic growth of E. coli. The growth rate of both S. aureus and E. coli was also reduced when both pathogens were co-incubated with B. longum lysate. The lysate of E. coli Nissle 1917 was only effective against S. pyogenes. The lysate of L. reuteri and E. coli Nissle 1917 were effective in improving the percentage viability of human epidermal keratinocyte (NHEKs) when these were co- incubated with S. aureus and S. pyogenes, respectively. Investigations of anti-biofilm activity showed that the lysate of L. reuteri was the only effective lysate in reducing biofilm formation but this effect was only manifested towards E. coli. For supernatants, the anti-biofilm effect was independent of acidity, where both the supernatant and neutralised supernatant of all used probiotics resulted in a significant reduction in biofilm formation by E. coli, and both the supernatant and neutralised supernatant of E. coli Nissle 1917 reduced the biofilm formation of P. aeruginosa. In conclusion, work presented in this doctoral thesis demonstrates promising effects of some probiotic-derived lysates and supernatants against both the planktonic and biofilm forms of specific wound-associated pathogens. This raises the possibility of introducing probiotic-derived products as anti-infectives in wound care.

Date of Award	1 Aug 2020
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Catherine O'Neill (Supervisor), Andrew Mcbain (Supervisor) & Sheena Cruickshank (Supervisor)