Research Projects

The global threat posed by rising Antimicrobial resistance (AMR) due to overuse of antibiotics has made it imperative to look for alternatives. Keeping in view the surge in emergence of antibiotic-resistant pathogens, The European Union has drafted the One Health Plan highlighting the link between human & animal health. WHO reports that the use of antibiotics is twice in livestock compared to humans, making livestock sector an urgent area of focus to combat AMR. Bovine mastitis is a challenge in dairy industry, predominantly caused by S. aureus and E.coli. Managing it accounts for 80% of the total antibiotics used in dairy industry. Hence, a priority area is looking for non-antibiotic therapeutics for treating bovine mastitis. This work will explore engineered Anti-Microbial Peptides (AMPs) as a non-antibiotic treatment for mastitis. AMPs are small peptides that act by disrupting cell membrane & have broad-spectrum antimicrobial activity. There are minimal chances of developing resistance to AMPs since they act by multiple mechanisms. In this work, we will develop template-based & de-novo engineered AMPs targeting S. aureus & E. coli. The objective is to create a safe & sustainable alternative to antibiotics by developing an AMP-based therapy that is antibacterial without promoting resistance. The hypothesis is that AMPs can target & kill antibiotic-resistant bacteria, but naturally occurring AMPs face challenges in clinical development that can be addressed by engineering them. Template-based & de-novo design will be used to optimise AMPs for better efficacy under biological conditions. Cyclisation of AMPs will be done, which can increase stability & eliminate need for supplementary delivery systems for in vivo use. Conjugating AMPs with liposomes/AgNPs can enhance their antimicrobial activity. All three forms of AMP systems will be evaluated in vitro & in vivo. Main Experiments: 1 AMP Synthesis & Characterization 2 Antibacterial efficiency of the AMPs against S. aureus & E. coli 3 Serum stability & thermal stability 4 Cytotoxicity on mammalian cells 5 Peptide cyclization using PyMOL & HADDOCK 6 Preparation & characterization of peptide-conjugated liposomes & AgNPs 7 Release kinetics of AMP-conjugate systems 8 Mammary organoid culture infected with S. aureus & E. coli for in vitro testing 9 In vivo mastitis model: S. aureus & E. coli-induced mastitis in Wistar rats & lactating cows with clinical mastitis will be used to assess AMP-based treatments compared to conventional antibiotics. Ethical approval will be obtained. Significance to the Field: This study will reduce reliance on conventional antibiotics & risk of antibiotic-resistant pathogens entering the food chain by developing an AMP-based therapy to combat bovine mastitis. Developing novel antibiotic alternatives supports the One Health approach & will lead to more sustainable livestock farming practices, contributing to both the Swasth Bharat initiative & global AMR mitigation efforts.