JODHPUR : Indian Institute of Technology Jodhpur researchers have conceptualized, designed, and synthesized an antimicrobial peptide molecule, SP1V3_1, that can kill gram-positive and gram-negative bacteria like E. coli, P. aeruginosa, K. pneumoniae, and MRSA (methicillin-resistant Staphylococcus aureus) by adopting a helical conformation while interacting with bacterial membranes. The peptide molecule has been found to be non-toxic based on various studies. The peptide was also found to promote wound healing in the murine model and prevent on-site post-surgical infections by MRSA.
In this design strategy our primary aim is to reduce toxicity of the snake venom without loosing its anti-microbial property. Thus, we truncated the snake venom peptide and eliminated the toxic part of snake venom. Further we stitched helical short peptide at N-terminus for the smooth entry of our newly designed therapeutic inside the bacterial cell.
Bacterial antibiotic resistance is a prevailing global menace that scientists must tackle worldwide. Most naturally occurring antimicrobial peptides have varying hydrophobicities and charge compositions, limiting their use as human therapeutic molecules despite their potent bacteria-killing ability. The researchers of IIT Jodhpur, Dr. Surajit Ghosh, Professor, Department of Bioscience & Bioengineering and Smart Healthcare Department along with Dr. Samya Sen, Mr. Ramkamal Samat, Dr. Moumita Jash, Mr. Satyajit Ghosh, Mr. Rajsekhar Roy, Ms. Nabanita Mukherjee, Mr. Surojit Ghosh and Dr. Jayita Sarkar have published this paper in the Journal of Medicinal Chemistry (DOI: https://doi.org/10.1021/acs.jmedchem.3c01150?urlappend=%3Fref%3DPDF&jav=VoR&rel=cite-as)
This invention takes care of two major problems:
- Firstly, the non-specific nature of the membranolytic ability of the peptides gives the bacteria very little chance to generate resistance against it.
- Secondly, it has a broad spectrum of activity i.e., it can effectively kill both gram-negative and gram-positive organisms like E. coli, P. aeruginosa, K. pneumoniae, and MRSA, maintaining good biocompatibility.
Talking about the end application of the invention, Dr. Surajit Ghosh, Professor, Department of Bioscience & Bioengineering and Smart Healthcare Department, IIT Jodhpur, said, “In the era of developmental stagnation of antibiotics due to the ever-increasing problem of antimicrobial resistance, antimicrobial peptides are exciting leads in the development of novel biocidal agents. The invented antimicrobial peptide SP1V3_1 holds the potential to be developed into a marketable pharmaceutical product, as and when it passes the requisite trials.”
He further added, “The peptide can therapeutically be implemented as a component of an ointment (alone or in combination with other drugs/peptides) for wound disinfection and healing, as an injectable/oral drug for systemic administration, or as an aerosolized formulation to treat a wide range of respiratory bacterial pathogens.”
This work has been provisionally e-filed for patenting in India [Indian Pat. Appl. (2022), IN 202211052566. Provisional Filed]. The work has received the grants by SERB, India, and SEED grant, IIT Jodhpur. As a future scope, the peptide SP1V3_1 can be further explored as an antiprotozoal or antifungal molecule. Due to the FLPII (antimicrobial and immunomodulatory) motif, SP1V3_1 can also be tested as an anticancer molecule in the future.
