BIOTECHNOLOGICAL DESIGN TO OPTIMIZE THE PRODUCTION OF BIOACTIVE LACTOBACILLUS PLANTARUM BY-PRODUCTS: NOVEL CHRONIC WOUND TREATMENT

Lactobacillus plantarum culture supernatants (LAPS) have antimicrobial, pro‐healing and anesthetic properties, so our medical team applied whole cultures and LAPS in chronic wounds with encouraging results. Metabolites responsible for LAPS properties and its action mechanism were previously determined. Objective: to design methods and culture media to increase the production of LAPS metabolites and optimize it´s therapeutic effectiveness. Modifications in MRS broth composition were made and L. plantarum was cultivated in the resulting different media with different physicochemical conditions to obtain modified supernatants (LAPS_m). Antimicrobial and anti-biofilm activity (crystal violet) of LAPS_m on strains typically isolated from chronic wounds (Pseudomonas aeruginosa, Staphylococcus aureus, Staphylococcus epidermidis and Serratiamarcescens), was tested. Concentration of barbiturates in LAPS_m was quantified by GCMS and its relative anesthetic potency in healthy volunteers was evaluated. DNAase and auto inducers type 2biological activity in LAPS_m were quantified. In addition, a safety assessment of LAPS_m application on healthy skin of 200 volunteers was performed. LAPS_m obtained from media with high concentrations of yeast extract possessed the greatest anesthetic power. Those containing greater amount of proteins, cations and surfactants had the highest capacity of biofilm disruption (p<0.01). When glucose and galactose concentration were increased in media, LAPS_m had the greatest antimicrobial power (p<0.05). Finally, there is great safety in the application of LAPS_m as no edema or erythema was observed. The results obtained will allow the manufacture of LAPS_m with greater therapeutic effectiveness and even custom properties for each type of wound