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Methods to Inhibit Bacterial Pyomelanin Production and Determine the Corresponding Increase in Sensitivity to Oxidative Stress
Published on: August 31, 2015
Essential oils modulate virulence phenotypes in a multidrug-resistant pyomelanogenic Pseudomonas aeruginosa clinical
Jayalekshmi Haripriyan1, Christy Rose Binu1, Nitasha D Menon1
1School of Biotechnology, Amrita Vishwa Vidyapeetham, Amritapuri, Kerala, India.
Abstract:
Pyomelanogenic P. aeruginosa, frequently isolated from patients with urinary tract infections and cystic fibrosis, possesses the ability to withstand oxidative stress, contributing to virulence and resulting in persistent infections. Whole genome sequence analysis of U804, a pyomelanogenic, multidrug-resistant, clinical isolate, demonstrates the mechanism underlying pyomelanin overproduction. Seven essential oils (EOs) were screened for pyomelanin inhibition. Garlic, cinnamon and thyme EOs were selected for further studies based on their significant anti-virulent properties, like inhibition of pyomelanin production and biofilm formation. Additionally, downregulation of the expression of virulence genes regulated by quorum sensing (QS) and a decrease in levels of the QS signaling molecule, C12-HSL, were also observed. The EO treatment inhibited the survival of U804 in human blood and increased survival of C. elegans, a whole animal model of pathogenesis. EO treatment also resulted in a significant reduction of efflux pump activity, indicative of their effect on antibiotic sensitization. Garlic oil enhanced the permeability of the bacterial membrane, resulting in decreased survival, when combined with sub-MIC concentrations of colistin. This study demonstrates that thyme, cinnamon and garlic EOs can attenuate pyomelanogenic P. aeruginosa virulence traits. Additionally, garlic potentiates drug sensitivity, suggesting its promising therapeutic use in combating pyomelanogenic MDR infections.
Insights
Essential oils from garlic, cinnamon, and thyme inhibit pyomelanin production and virulence in multidrug-resistant Pseudomonas aeruginosa. These natural compounds also enhance antibiotic effectiveness, offering a promising strategy against persistent infections.
Area of Science:
- Microbiology
- Natural Products Chemistry
- Infectious Diseases
Background:
- Pyomelanogenic Pseudomonas aeruginosa causes persistent infections, particularly in urinary tract infections and cystic fibrosis, due to its oxidative stress resistance.
- Multidrug resistance (MDR) in P. aeruginosa complicates treatment strategies.
- Understanding the mechanisms of pyomelanin overproduction is crucial for developing novel therapies.
Purpose of the Study:
- To investigate the anti-virulence properties of essential oils (EOs) against pyomelanogenic, multidrug-resistant P. aeruginosa.
- To elucidate the effects of EOs on pyomelanin production, biofilm formation, and quorum sensing (QS).
- To evaluate the potential of EOs in combination with antibiotics to combat P. aeruginosa infections.
Main Methods:
- Whole genome sequencing of a clinical isolate (U804) to understand pyomelanin overproduction.
- Screening of seven essential oils for pyomelanin inhibition.
- Assessing anti-virulence effects including biofilm inhibition, QS modulation, and in vivo efficacy in human blood and C. elegans models.
- Evaluating efflux pump activity and bacterial membrane permeability.
Main Results:
- Garlic, cinnamon, and thyme EOs significantly inhibited pyomelanin production and biofilm formation.
- EO treatment downregulated QS-regulated virulence genes and reduced C12-HSL levels.
- EOs reduced bacterial survival in human blood and enhanced survival in C. elegans.
- EOs decreased efflux pump activity and, in the case of garlic oil, increased bacterial membrane permeability, potentiating colistin efficacy.
Conclusions:
- Thyme, cinnamon, and garlic EOs effectively attenuate pyomelanogenic P. aeruginosa virulence factors.
- These EOs offer a potential therapeutic approach to combat persistent and multidrug-resistant P. aeruginosa infections.
- Garlic oil shows promise in enhancing antibiotic sensitivity, suggesting synergistic therapeutic applications.
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