Development of a Quorum-Sensing Based Bacterial GMO for Targeted Treatment of Bovine Mastitis.

Abstract

Bovine mastitis, a prevalent and costly disease affecting dairy cows, severely impacts milk production, quality, and cow health and poses significant challenges to the dairy industry worldwide. Traditional treatment strategies relying on antibiotics face concerns of antibiotic resistance and residual antibiotic residues in dairy products. Therefore, there is an urgent need for innovative and sustainable approaches. Our study undertakes a preliminary investigation into the formulation and efficacy of a GMO-based antibiotic-free treatment in fighting Bovine mastitis. We propose to use the bioengineered defensin Nisin PV as the antimicrobial to specifically target the causative pathogen Staphylococcus aureus. To disrupt the biofilm formation, we have leveraged the potency of DNaseI. By hacking the quorum sensing technique of Staphylococcus aureus, our proposed genetically modified bacteria would sense the presence of pathogens and initiate their eradication by producing Nisin PV and DNaseI. Results show the efficacy of DNase I against bacterial biofilm formation, in addition to the efficacy of our proposed sensor, which is based on the agr quorum sensing system of Staphylococcus aureus, a major cause of bovine mastitis. Molecular dynamics and simulations show that our choice of the bacterial defensin, Nisin PV, is less susceptible to cleavage by bacterial strains resistant to the native bacteriocin Nisin A. Additionally, we theoretically propose a lysis-based kill switch to ensure the release of the therapeutic components. The solution proposed in this study has the potential to offer a sustainable and effective alternative to antibiotic-based treatments. Implementation of bioengineered defensins could reduce disease incidence, minimize economic losses, and promote responsible antimicrobial stewardship in the dairy industry.