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.

Microbial Pathogenesis
|October 20, 2022
PubMed
Abstract

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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