Botulinum Neurotoxin A Enhances Recovery from Bacterial Skin Infections

Abstract

Bacterial skin and soft tissue infections (SSTIs) are major causes to human suffering, morbidity, and mortality worldwide. The majority of SSTIs are caused by the gram-positive bacterial pathogens including Staphylococcus aureus, and Streptococcus pyogenes. Although not as common as gram-positive infections, gram-negative pathogens such as Pseudomonas aeruginosa are also becoming more prevalent. Currently, antibiotics are the only and most common treatment for bacterial SSTIs. However, the rise in antibiotic resistance within bacterial pathogens poses a significant threat to global healthcare. In addition, long-term antibiotic use is linked to a variety of adverse consequences. Here, we investigated the efficiency of onabotulinumtoxinA (onabotA), a clinical formulation of botulinum neurotoxin A (BoNT/A) as a treatment for SSTIs in mouse models infection with both gram-positive (S. aureus and S. pyogenes) and gram-negative bacteria (P. aeruginosa) bacterial pathogens. We show that treatment with onabotA improves the outcome of both gram-positive and gram-negative skin infections. OnabotA reduced skin abscess and lesion sizes, modulated immune cell populations, limited inflammation, and promoted tissue remodeling. These finding demonstrate that onabotA improves disease outcomes in SSTIs mouse models and shows high potential as a novel therapeutic strategy for treating bacterial skin infections.