In Vivo Acute Toxicity and Therapeutic Potential of a Synthetic Peptide, DP1 in a Staphylococcus aureus Infected Murine Wound Excision Model

Bacterial infections at the surgical sites are one of the most prevalent skin infections that impair the healing mechanism. They account for about 20% of all types of infections and lead to approximately 75% of surgical-site infection-associated mortality. Several antibiotics, such as cephalosporins, fluoroquinolones, quinolones, penicillin, sulfonamides, etc., that are used to treat such wound infections not only counter infections but also disrupt the normal flora. Moreover, antibiotics, when used for a prolonged duration, may impair the formation of new blood vessels, delay collagen production, or inhibit the migration of certain cells involved in wound repair, leading to an impaired healing process. Therefore, there is a dire need for alternate therapeutic approaches against such infections. Antimicrobial peptides have gained considerable attention as a promising strategy to counter these pathogens and prevent the spread of infection. Recently, we have reported a designed peptide, DP1, and its broad-spectrum in vitro antimicrobial activity against Gram-positive and Gram-negative bacteria. In the present study, in vivo acute toxicity of DP1 was evaluated and even at a high dose (20 mg/kg body weight) of DP1, a 100% survival of mice was observed. Subsequently, a Staphylococcus aureus-infected murine wound excision model was established to assess the wound healing efficacy of DP1. The study revealed significant wound healing vis-a-vis attenuated S. aureus bioburden at the wound site and also controlled the oxidative stress depicting anti-oxidant activity as well. Healing of the infected wounds was also verified by histopathological examination. Based on the results of this study, it can be concluded that DP1 improves wound resolution despite infections and promotes the healing mechanism. Hence, DP1 holds compelling potential as a novel antimicrobial drug that requires further explorations in clinical platforms.

Automated summary

Bacterial infections at surgical sites are common and have high mortality rates. Traditional antibiotics not only disrupt the normal flora, but also delay wound healing. Therefore, alternative therapies are needed. Antimicrobial peptides have gained attention as a promising strategy to combat these infections.