Researchers Develop Multi-model Nanobiotic Platform Combatting Multidrug-resistant Pathogens
Surmounting the challenge to develop a novel arsenal against bacterial pathogens remains formidable. However, a research team fromIndian Institute of Technology Roorkee (IIT Roorkee) employed a strategy to develop a multimodal nanobiotic platform which combats bacterial pathogens. The nanoplatform leverages the synergistic antibacterial activity of a food-grade peptide (an antimicrobial peptide from Generally Recognised As Safe- GRAS category bacterium, Pediococcus pentosaceus) to mitigate multidrug-resistant bacterial pathogens. The technology platform has been shown to have applications in health sector and food packaging.
The team used pediocin; a class IIa bacteriocin to decorate silver (Ag°) nanoparticles and developed a double-edged nano-platform (Pd-SNPs) that inherits intrinsic properties of both antibacterial moieties, which engenders strikingly high antibacterial potency against a broad spectrum of bacterial pathogens including the ESKAPE category (six antibiotic-resistant bacterial pathogens) without displaying adverse cytotoxicity to mammalian cells. The enhanced antimicrobial activity of Pd-SNPs is due to their higher affinity with the bacterial cell wall, which allows Pd-SNPs to penetrate the outer membrane, inducing a shift in electric charge distribution of the membrane cell leading to the disruption of membrane integrity. A battery of genetic regulatory elements based rapid and sensitive screening tool for mechanism of action assessment revealed that the upregulation of cpxP, degP and sosX genes triggers the burst of reactive oxygen species which eventually cause bacterial cell death. These findings underscore new avenues for using a potent biocompatible nanobiotic platform to combat a wide range of bacterial pathogens.
All animal experiments were conducted in compliance with the Institutional Animal Ethics Committee of the IIT Roorkee, according to the guidelines of the Committee for the Purpose of Control and Supervision of Experiments on Animals (Government of India, New Delhi).
The research team that contributed to the study from IIT Roorkee are Prof. Naveen Kumar Navani, Chemical Biology Laboratory, Department of Biosciences and Bioengineering and Adjunct Faculty, Centre of Nanotechnology, IIT Roorkee; Piyush Kumar, Arshad Ali Shaikh, Pardeep Kumar, Rajat Dhyani, Tarun Kumar Sharma, Ajmal Hussain, Chemical Biology Laboratory, Department of Biosciences and Bioengineering, IIT Roorkee; Vivek Kumar Gupta, Ranjana Pathania, Molecular Bacteriology and Chemical Genetics Laboratory, Department of Biosciences and Bioengineering, IIT Roorkee; Krishnakant Gangele, Krishana Mohan Poluri, Mechanistic Biological Chemistry Laboratory, Department of Biosciences and Bioengineering, IIT Roorkee.
“I would like to congratulate the research team at IIT Roorkee for their novel idea towards developing a vehicle to mitigate persistant bacterial infections. This will open up new avenues for combating a wide range of pathogens in the health or food sector,” Prof Ajit K Chaturvedi, Director, IIT Roorkee, said.
Prof Naveen Kumar Navani and Piyush Kumar conceptualised the research and wrote the research paper; Piyush Kumar, Arshad Ali Shaikh, Pardeep Kumar, Vivek Kumar Gupta, Rajat Dhyani, Tarun Kumar Sharma, Ajmal Hussain, performed the research. The findings have been published in the American Chemical Society Journal-ACS Applied Materials and Interfaces.
Prof Naveen Kumar Navani, Chemical Biology Laboratory, Department of Biosciences and Bioengineering and Adjunct Faculty, Centre of Nanotechnology, IIT Roorkee, highlighted, “Pd-SNPs, a nanobiotic platform serving a variety of biomedical uses, display unprecedented advantages because they are heat-resistant, retain antibacterial activity in human serum, and alleviate vancomycin-intermediate Staphylococcus aureus (VISA) infection in the mouse model. In addition, Pd-SNPs wrapped in biodegradable nanofibers mitigated Listeria monocytogenes in cheese samples. It is interesting that the synergistic interaction of SNPs with pediocin would also lead to a significant decrease in toxicity associated with silver ions, which is a critical criterion for biomedical applications."
Dr Piyush Kumar, Post-doctoral Fellow, Chemical Biology Laboratory, Department of Biosciences and Bioengineering, IIT Roorkee, lead author of the paper said, “One of the attributes of a potent arsenal against MDR pathogens is long-lasting antibacterial efficacy. We investigated the ability of L monocytogenes and VISA-ST1745 (specific types of antimicrobial-resistant bacteria) to acquire resistance against Pd-SNPs which displayed that bacterial pathogens were failed to evolve resistance against Pd-SNPs. The developed Pd-SNPs showed excellent biocompatibility when exposed to different mammalian cells. Furthermore, the results revealed that Pd-SNPs reduced the cellular invasion which shows that Pd-SNPs are able to reduce the virulence of clinical pathogens and invasiveness of both the clinical antibiotic-resistant Staphylococcus aureus pathogen.”
This research was supported by funding from Scheme for Transformational and Advanced Research in Sciences (STARS) initiative of Ministry of Education, Govt of India.
