Sequence similarity searches for morphine biosynthesis enzymes in bacteria yield putative targets for understanding associations between infection and opiate administration

Exploiting the immunosuppressive, analgesic and highly addictive properties of morphine could increase the success of a bacterial pathogen. Therefore, we performed sequence similarity searches for two morphine biosynthesis demethylases in bacteria. For thebaine 6-O-demethylase and codeine O-demethylase, we found strong alignments to three ( Pseudomonas aeruginosa , Klebsiella pneumoniae and Acinetobacter baumannii ) of the six ESKAPE pathogens ( Enterococcus faecalis , Staphylococcus aureus , K. pneumoniae , A. baumannii , P. aeruginosa and Enterobacter species) that are commonly associated with drug resistance and nosocomial infections. Expression of the aligned sequence found in P. aeruginosa (NP_252880.1/PA4191) is upregulated in isolates obtained from cystic fibrosis patients. Our findings provide putative mechanistic targets for understanding the role of morphine in pathogenicity.