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Updated: Jul 12, 2025
A Mouse Model to Assess Innate Immune Response to Staphylococcus aureus Infection
Published on: February 28, 2019
In Vivo Acute Toxicity and Therapeutic Potential of a Synthetic Peptide, DP1 in a Staphylococcus aureus Infected
Panchali Barman1, Chakshu Sharma2, Shubhi Joshi2
1Institute of Forensic Science and Criminology (UIEAST), Panjab University, Chandigarh, 160014, India.
Abstract:
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.
Insights
A novel antimicrobial peptide, DP1, effectively treats bacterial wound infections and promotes healing. This peptide shows low toxicity and significant efficacy in vivo, offering a promising alternative to traditional antibiotics for surgical site infections.
Area of Science:
- Microbiology
- Biomedical Engineering
- Dermatology
Background:
- Surgical site infections (SSIs) are a major cause of morbidity and mortality, often treated with antibiotics that disrupt normal flora and impair wound healing.
- Existing antibiotics pose risks, including resistance and adverse effects on tissue repair processes like angiogenesis and collagen synthesis.
- There is a critical need for alternative therapeutics that can combat bacterial infections without compromising the wound healing cascade.
Purpose of the Study:
- To evaluate the in vivo acute toxicity and wound healing efficacy of a designed antimicrobial peptide, DP1.
- To assess DP1's impact on bacterial burden, oxidative stress, and histopathological changes in a Staphylococcus aureus-infected murine wound model.
- To determine the potential of DP1 as a novel therapeutic agent for infected wounds.
Main Methods:
- In vivo acute toxicity testing of DP1 in mice at a dose of 20 mg/kg body weight.
- Establishment of a Staphylococcus aureus-infected murine wound excision model to evaluate DP1's therapeutic effect.
- Assessment of wound healing, bacterial load, oxidative stress markers, and histopathological changes post-treatment with DP1.
Main Results:
- DP1 demonstrated excellent safety, with 100% survival observed in mice even at a high dose.
- DP1 significantly accelerated wound healing and reduced Staphylococcus aureus bioburden at the infection site.
- The peptide also exhibited antioxidant activity, controlling oxidative stress, and promoted healing confirmed by histopathology.
Conclusions:
- DP1 is a safe and effective antimicrobial agent that promotes wound healing in the presence of bacterial infection.
- DP1's dual action of combating infection and enhancing tissue repair makes it a promising candidate for clinical development.
- Further clinical investigations are warranted to explore DP1's full therapeutic potential for managing infected wounds.
