In our ever-evolving battle against drug-resistant pathogens, the search for novel and safe drugs has become an urgent necessity. One such resilient adversary is Serratia marcescens, a multidrug-resistant bacterium responsible for a range of healthcare-associated infections. To combat this growing threat, it’s time to shift our focus from simply inhibiting bacterial growth to targeting bacterial virulence – a strategy that could reduce antimicrobial resistance and bolster the host’s immune response. Enter Bergamot Essential Oil (BEO), a hidden gem in nature’s pharmacy. In this blog, we delve into a fascinating exploration of BEO’s major phytocompounds and their potential to combat virulent proteins produced by S. Marcescens.
The Power of Natural Therapies
Overuse and misuse of antibiotics have led to the rise of multidrug-resistant strains of bacteria that exhibit enhanced virulence. These formidable foes employ quorum-sensing signalling networks to regulate virulence factors, form biofilms, and thrive on both living and non-living surfaces. With a shortage of effective antibiotics in the pharmaceutical pipeline, the global healthcare community is turning to natural therapies as a promising alternative. These therapies, including medicinal and aromatic plants, offer safety, minimal toxicity, eco-friendliness, and a lack of adverse side effects.
Bergamot Essential Oil: A Medicinal Marvel
Citrus bergamia, commonly known as bergamot, is a treasure trove of medicinal and aromatic properties. The fruit of this plant is the source of Bergamot Essential Oil (BEO), renowned for its rich composition of furanocoumarins and terpenes. Among its key constituents are limonene and linalyl acetate. BEO boasts an impressive array of therapeutic benefits, making it a sought-after ingredient in cosmetics, perfumes, and various medicinal applications. It is recognized for its antimicrobial, anti-inflammatory, anti-proliferative, analgesic, neuroprotective, and anti-cancer activities.
Serratia marcescens: A Formidable Foe
Serratia marcescens, a human pathogen of great concern, is responsible for life-threatening infections such as urinary tract infections, pneumonia, endocarditis, bloodstream infections, and meningitis. Its multidrug resistance presents a significant challenge, and it is equipped with a wide range of virulent factors, including proteases and enzymes involved in quorum-sensing signalling pathways, allowing it to thrive in various environments.
Targeting Virulence: Serralysin and FabI
In the intricate web of bacterial infection, bacterial proteases, often overlooked, play a crucial role in virulence. These enzymes are indispensable for bacterial replication, survival, and pathogenicity. Serratia marcescens produces serralysin, a zinc metalloprotease, which degrades host-derived antimicrobial proteins, facilitating bacterial invasion and dissemination. Similarly, FabI, a reductase enzyme involved in fatty acid synthesis, contributes to quorum-sensing signalling pathways. Inhibiting FabI is a promising strategy to combat bacterial infections.
Computational Docking: A Powerful Tool
To identify potential drug candidates within BEO, we conducted a sophisticated computational analysis. Gas chromatography-mass spectrometry (GC-MS) provided insights into the major phytocompounds in BEO. We then employed molecular docking simulations to assess how these compounds interacted with Serratia protease and FabI. The results were promising, revealing strong binding interactions, particularly with Linalool, which exhibited binding energies of -3.130 kcal/mol and -3.939 kcal/mol for Serratia protease and FabI, respectively.
A Promising Path Forward
Our findings suggest that BEO phytocompounds hold great promise as potential drug candidates. This research marks a significant step toward developing plant-based compounds as inhibitors of virulent proteins in multidrug-resistant S. Marcescens. By targeting bacterial virulence rather than merely inhibiting growth, we aspire to make significant strides in the fight against multidrug-resistant pathogens. Additionally, this approach could empower the host’s defence mechanisms, enhancing the ability to clear infections.
Conclusion
As multidrug-resistant bacteria continue to pose a significant threat to public health, it is evident that the era of traditional antibiotics is waning. In this challenging landscape, Bergamot Essential Oil (BEO) emerges as a beacon of hope. Our research reveals its potential to combat the virulence of Serratia marcescens through the inhibition of key bacterial proteins. By harnessing the power of nature, we are taking a step closer to developing innovative solutions to address this pressing global health issue.
Authors
Ananya Mishra, Navya Tyagi, Shruti Srivastava, Soumya Bhatia, Kshitija Talwekar; B. Tech. Biotechnology, Third year, Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Pune.