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Author Spotlight: Advancing Therapeutics to Treat Vibriosis in Humans and Aquatic Organisms
Published on: May 31, 2024
6-Methylcoumarin rescues bacterial quorum sensing induced ribosome-inactivating stress in Caenorhabditis elegans
Poornima Ramesh1, Sukesh Kumar Bajire2, Anagha Kanichery1
1Center for Systems Biology and Molecular Medicine, Yenepoya Research Centre, Yenepoya (Deemed to be University), University Road, Deralakatte, Mangalore, 575018, India.
Introduction:
Bacterial pathogenicity has for long posed severe effects on patient care. Pseudomonas aeruginosa is a common cause of hospital-acquired infections and nosocomial illnesses. It is known to infect the host by colonizing through quorum sensing and the production of exotoxins.
Methods:
The current effort is an analysis of proteomic alterations caused by P. aeruginosa PAO1 to study the effects of quorum sensing inhibitor 6-Methylcoumarin on PAO1 infectivity in the Caenorhabditis elegans model.
Results:
Through tandem mass tag-based quantitative proteomics approaches, 229 proteins were found to be differentially regulated in infection and upon inhibition. Among these, 34 proteins were found to be dysregulated in both infection and quorum-sensing inhibition conditions. Along with the dysregulation of proteins involved in host-pathogen interaction, PAO1 was found to induce ribosome-inactivating stress accompanied by the downregulating mitochondrial proteins. This in turn caused dysregulation of apoptosis. The expression of multiple proteins involved in ribosome biogenesis and structure, oxidative phosphorylation, and mitochondrial enzymes were altered due to infection. This mechanism, adapted by PAO1 to survive in the host, was inhibited by 6-Methylcoumarin by rescuing the downregulation of ribosomal and mitochondrial proteins.
Conclusions:
Taken together, the data reflect the molecular alterations due to quorum sensing and the usefulness of inhibitors in controlling pathogenesis.
Insights
Quorum sensing inhibitor 6-Methylcoumarin effectively reduced Pseudomonas aeruginosa pathogenicity by restoring ribosomal and mitochondrial protein levels in a Caenorhabditis elegans model. This study highlights the potential of quorum sensing inhibitors in combating bacterial infections.
Area of Science:
- Microbiology and Proteomics
- Host-Pathogen Interactions
- Drug Discovery and Development
Background:
- Bacterial pathogenicity, particularly from *Pseudomonas aeruginosa*, significantly impacts patient care, leading to hospital-acquired infections.
- *Pseudomonas aeruginosa* utilizes quorum sensing and exotoxins for host colonization and infection.
- Understanding the molecular mechanisms of *P. aeruginosa* infection is crucial for developing effective therapeutic strategies.
Purpose of the Study:
- To analyze proteomic alterations induced by *P. aeruginosa* PAO1 infection.
- To investigate the impact of the quorum sensing inhibitor 6-Methylcoumarin on PAO1 infectivity.
- To elucidate the molecular mechanisms underlying *P. aeruginosa* pathogenesis and inhibition using a *Caenorhabditis elegans* model.
Main Methods:
- Quantitative proteomics using tandem mass tag (TMT) analysis to identify differentially regulated proteins.
- Comparative proteomic profiling of *P. aeruginosa* PAO1 infected *C. elegans* with and without 6-Methylcoumarin treatment.
- Analysis of proteins involved in host-pathogen interaction, ribosome function, mitochondrial activity, and apoptosis.
Main Results:
- A total of 229 proteins were differentially regulated upon infection and inhibition; 34 were dysregulated under both conditions.
- *P. aeruginosa* PAO1 infection induced ribosome-inactivating stress and downregulated mitochondrial proteins, leading to apoptosis dysregulation.
- 6-Methylcoumarin inhibited PAO1's survival mechanism by rescuing the downregulation of ribosomal and mitochondrial proteins.
Conclusions:
- The study reveals key molecular alterations driven by quorum sensing in *P. aeruginosa* pathogenesis.
- Quorum sensing inhibitors, such as 6-Methylcoumarin, demonstrate significant potential in controlling bacterial pathogenesis.
- Targeting quorum sensing pathways offers a promising strategy for combating *P. aeruginosa* infections.
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