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

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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.

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Data Availability

The datasets generated or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

The author acknowledges the central instrumental facilities provided by SAIF/CIL, Panjab University, Chandigarh, India.

Funding

The study reported here was funded by DRDO, India and DST – FIST sanctioned to Department of Biophysics, Panjab University, India.

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Authors and Affiliations

  1. Institute of Forensic Science and Criminology (UIEAST), Panjab University, Chandigarh, 160014, India

    Panchali Barman

  2. Department of Biophysics, Panjab University, Chandigarh, U.T, 160014, India

    Chakshu Sharma, Shubhi Joshi, Sheetal Sharma, Mayank Maan, Neha Singla & Avneet Saini

  3. Department of Microbiology, Panjab University, Chandigarh, U.T, 160014, India

    Praveen Rishi

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Contributions

P.B. and C.S. performed the experiments, P.B. compiled the main manuscript, S.J., S.S. and M.M. aided in interpretation of the results. P.R. and N.S. provided valuable inputs during manuscript preparation. A.S. designed the study, supervised all experiments during manuscript preparation, contributed to discussion and reviewed the manuscript.

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Correspondence to Avneet Saini.

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Highlights

• Novel antimicrobial peptide DP1 is a promising alternative treatment to conventional antibiotics.

• DP1 is significantly less toxic as evident by its larger therapeutic window.

• Higher efficacy in healing Staphylococcus aureus infection wounds.

• DP1 reduces the Staphylococcus aureus colonization and bioburden contamination in wound infections.

• Regulates antioxidant levels and restores wound tissue.

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Barman, P., Sharma, C., Joshi, S. et al. In Vivo Acute Toxicity and Therapeutic Potential of a Synthetic Peptide, DP1 in a Staphylococcus aureus Infected Murine Wound Excision Model. Probiotics & Antimicro. Prot. (2023). https://doi.org/10.1007/s12602-023-10176-1

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