Probing the nano-therapeutic potential of super cationic carbon quantum dots for combating the bovine mastitis associated multi-drug resistant pathogens
Implementing Organization
Icar- National Dairy Research Institute, Regional Station
Principal Investigator
Dr. Basavaprabhu H N
Icar- National Dairy Research Institute, Regional Station
basavaprabhu73@gmail.com
Project Overview
The emergence and rapid spread of drug-resistant zoonotic pathogens within the dairy production chain presents a serious threat to both human health and food security. Mastitis, the most common bacterial infection in dairy cattle, has become increasingly difficult-to-treat due to the surge in bacterial antibiotic resistance. Manifestations of multi-drug resistant critical and high priority pathogens such as Methicillin Resistant Staphylococcus aureus (MRSA), Extended Spectrum Beta-Lactamase (ESBL) producing E. coli and multi-drug resistant Klebsiella spp. have been reported in the mastitis cases. This urges to rationalize the use of antibiotics in the veterinary medicine and calls for discovery of alternatives-to-antibiotics (ATA) to curb the menace of resistant infections and to avoid further escalation of resistance. Amongst the several alternatives, carbon quantum dots (CQDs) are emerging as frontiers in nano-medicine and microbial bio-control strategies due to their outstanding anti-microbial properties. CQDs are a novel class of zero-dimensional, fluorescent nanomaterials with the potential to serve as next-generation antimicrobial agents due to multi-mode of bacterial inhibition, low toxicity, high water dispersibility, excellent biocompatibility, and cost-effective synthesis. Given the urgency to unravel the novel ATA in dairy production system, the present project has been designed investigate the nanotherapeutic potential of CQDs for combating the bovine mastitis associated critical and high priority AMR pathogens of public health importance. This project uniquely focuses on exploring super cationic CQDs (high density of positive charges), hypothesizing that these modified nanomaterials will exhibit superior antimicrobial properties due to enhanced interaction with negatively charged bacterial cell and thereby potentiating the membrane disruption, cellular uptake, ROS generation, and biofilm disruption, against anti-microbial resistant (AMR) pathogens. The primary objectives are to fabricate and characterize super cationic CQDs, assess their antimicrobial activity and their mechanism of actions against critical and high priority AMR pathogens (ESBL E. coli and MRSA and Klebsiella spp.) in-vitro, and evaluate their safety through in-vitro cell line and in-vivo murine models. Therapeutic doses of CQDs will then be tested via intramammary administration using AMR pathogens induced mastitis murine model. In addition, CQD based hydrogel will be developed and evaluated as post milking teat dip for the prevention of mastitis cases in dairy cows. Thus, this project provides comprehensive pre-clinical safety, mechanistic, and therapeutic insights into the action of CQDs in combating the mastitis causing AMR pathogens for their futuristic clinical applications. Overall, this research aligns with the One Health approach by offering a groundbreaking, safer, nanotherapeutic strategy using CQDs to combat zoonotic AMR in dairy animals.