Sequence similarity searches for morphine biosynthesis enzymes in bacteria yield putative targets for understanding

Shing Hei Zhan1, Leon French2,3,4,5

  • 11 Department of Zoology, University of British Columbia, Vancouver, Canada.

Insights

Morphine

Area of Science:

  • Microbiology
  • Biochemistry
  • Pathogenesis

Background:

  • Morphine's immunosuppressive and analgesic properties may enhance bacterial pathogen success.
  • ESKAPE pathogens are significant contributors to drug resistance and hospital-acquired infections.
  • Understanding microbial interactions with host-derived compounds is crucial for novel therapeutic strategies.

Purpose of the Study:

  • To investigate the presence of bacterial morphine biosynthesis demethylases.
  • To identify potential roles of these enzymes in bacterial pathogenicity.
  • To explore the link between morphine metabolism and ESKAPE pathogen virulence.

Main Methods:

  • Sequence similarity searches were conducted for thebaine 6-O-demethylase and codeine O-demethylase.
  • Bioinformatic analysis identified alignments in key ESKAPE pathogens.
  • Gene expression analysis was performed on bacterial isolates from cystic fibrosis patients.

Main Results:

  • Strong sequence alignments were found in Pseudomonas aeruginosa, Klebsiella pneumoniae, and Acinetobacter baumannii.
  • The gene encoding the P. aeruginosa demethylase (NP_252880.1/PA4191) showed upregulated expression in cystic fibrosis isolates.
  • These findings suggest a potential role for bacterial morphine metabolism in pathogen adaptation and virulence.

Conclusions:

  • Bacterial morphine biosynthesis demethylases are present in critical ESKAPE pathogens.
  • Upregulated expression in P. aeruginosa suggests a role in specific host environments like cystic fibrosis.
  • These enzymes represent potential targets for understanding and combating bacterial infections.

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