Nisina como estratégia alternativa frente à resistência antimicrobiana: potencial terapêutico e abordagem in vitro entre mastite bovina e otite externa canina

Abstract

Antimicrobial resistance and biofilm formation stand out among the main factors associated with recurrence, chronicity, and therapeutic failure, highlighting the need for the development of alternatives with antimicrobial and antibiofilm potential capable of overcoming virulence and antimicrobial resistance. Given the limited availability of new pharmacological options, antimicrobial peptides such as nisin - a lantibiotic bacteriocin produced by Lactococcus lactis - have been investigated as therapeutic alternatives. Therefore, the present study aimed to evaluate the antimicrobial and antibiofilm activity, as well as the toxicity profile, of nisin against bacteria isolated from cases of canine otitis externa and bovine mastitis, in order to explore its potential in addressing AMR. In the first experiment, 34 bacterial isolates obtained from dogs diagnosed with otitis externa were evaluated, including Corynebacterium spp. and coagulase-negative Staphylococcus spp. Following microbiological identification and antimicrobial susceptibility testing, the minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), growth curve, and time-kill assays were determined. The biofilm-forming ability of the included pathogens was also assessed, as well as the capacity of nisin to inhibit and eradicate preformed biofilms. Toxicity was assessed using the hemolysis assay. Nisin exhibited predominantly bacteriostatic and transient activity, with greater efficacy during the early stages of biofilm formation. Hemolysis rates remained below the threshold considered toxic, indicating a favorable safety profile for clinical application. In the second project, 25 Staphylococcus aureus isolates obtained from cases of bovine mastitis were evaluated. Antimicrobial susceptibility profile, biofilm production capacity, MIC, MBC, and biofilm inhibition and eradication assays were performed. Nisin demonstrated antimicrobial activity against the evaluated isolates, with a dose-dependent effect and greater impact on inhibiting biofilm formation compared to the eradication of established biofilms. A significant reduction in bacterial viability and biofilm biomass was observed at specific concentrations. In summary, the results indicate that nisin shows potential as an adjuvant strategy for controlling bacterial infections associated with canine otitis externa and bovine mastitis, particularly due to its action on the early stages of biofilm formation. Despite its predominantly bacteriostatic activity and reduced efficacy against mature biofilms, its low toxicity profile and ability to interfere with bacterial persistence reinforce its relevance as a promising alternative in the context of antimicrobial resistance.