Abstract
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.
Highlights
Several parasites are known to cause behavioural changes in their hosts
Beyond the devastating effects on the developing nervous system, T. gondii infection is associated with schizophrenia [3, 4], which has long been associated with dopamine, including a genome-wide significant association in the dopamine receptor 2 gene [5]
Across the protein sequences translated from these genomes, we searched for the sequences of two enzymes involved in morphine biosynthesis to understand the associations between infection and opiates
Summary
Several parasites are known to cause behavioural changes in their hosts. Studies on the molecular mechanisms that are altered by these parasites are lacking. A bioinformatic analysis discovered two genes that encode tyrosine hydroxylase in the genome of the Toxoplasma gondii parasite These enzymes were found to have substrate specificity [1]. Beyond the devastating effects on the developing nervous system, T. gondii infection is associated with schizophrenia [3, 4], which has long been associated with dopamine, including a genome-wide significant association in the dopamine receptor 2 gene [5] Such findings, which began with bioinformatics analyses, provide target mechanisms for understanding how parasites alter host behaviour. Such efforts are supported by the availability of thousands of genomes that catalogue the wide diversity of bacterial pathogens [11, 12]. Across the protein sequences translated from these genomes, we searched for the sequences of two enzymes involved in morphine biosynthesis to understand the associations between infection and opiates
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