Targeting neuro-immune signaling to treat bacterial infections

Bacterial skin and soft tissue infections (SSTIs) are increasingly common due to the rise in prevalence of multi-drug resistant pathogens, necessitating novel non-antibiotic based treatments. While methicillin-resistantStaphylococcus aureus (MRSA) and Streptococcus pyogenesare the two leading causes of SSTIs, up to 20% of SSTIs are also caused by gram-negative bacteria. We have found that skin-innervating neurons play a key role in suppressing neutrophil function and the innate immune response against SSTIs. We have developed an approach to treat bacterial infections by targeting this neuro-immune axis using botulinum neurotoxins (BoNTs) serotype A and serotype E, thereby blocking neuro-immune signaling and enhancing host immunity. In this project, we determine whether this therapeutic approach is broadly applicable by testing BoNTs against S. pyogenes, MRSA, and P. aeruginosa infections. We are in active discussions to partner with companies that produce both of these products. Utilizing BoNTs to enhance host immunity could be a transformative approach to treat challenging bacterial infections.