1887

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.

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2019-05-20
2021-07-24
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References

  1. Gaskell EA, Smith JE, Pinney JW, Westhead DR, McConkey GA. A unique dual activity amino acid hydroxylase in Toxoplasma gondii. PLoS One 2009; 4:e4801 [View Article]
    [Google Scholar]
  2. Prandovszky E, Gaskell E, Martin H, Dubey JP, Webster JP et al. The neurotropic parasite Toxoplasma gondii increases dopamine metabolism. PLoS One 2011; 6:e23866 [View Article]
    [Google Scholar]
  3. Fuglewicz AJ, Piotrowski P, Stodolak A. Relationship between toxoplasmosis and schizophrenia: a review. Adv Clin Exp Med 2017; 26:1033–1038 [View Article]
    [Google Scholar]
  4. Burgdorf KS, Trabjerg BB, Pedersen MG, Nissen J, Banasik K et al. Large-scale study of Toxoplasma and cytomegalovirus shows an association between infection and serious psychiatric disorders. Brain Behav Immun 2019 29 Jan 2019 [View Article]
    [Google Scholar]
  5. Schizophrenia Working Group of the Psychiatric Genomics Consortium Biological insights from 108 schizophrenia-associated genetic loci. Nature 2014; 511:421–427 [View Article]
    [Google Scholar]
  6. Hernandez MC, Flores LR, Bayer BM. Immunosuppression by morphine is mediated by central pathways. J Pharmacol Exp Ther 1993; 267:1336–1341
    [Google Scholar]
  7. Hagel JM, Facchini PJ. Dioxygenases catalyze the O-demethylation steps of morphine biosynthesis in opium poppy. Nat Chem Biol 2010; 6:273–275 [View Article]
    [Google Scholar]
  8. Goumon Y, Casares F, Pryor S, Ferguson L, Brownawell B et al. Ascaris suum, an intestinal parasite, produces morphine. J Immunol 2000; 165:339–343 [View Article]
    [Google Scholar]
  9. Mostafaei TS, Naem S, Imani M, Dalirezh N. Evidence for the presence of morphine like substance and μ opiate receptor expression in Dicrocoelium dendriticum (Trematoda: Dicrocoeliidae). J Hell Vet Med Soc 2018; 68:385–390 [View Article]
    [Google Scholar]
  10. Vouga M, Greub G. Emerging bacterial pathogens: the past and beyond. Clin Microbiol Infect 2016; 22:12–21 [View Article]
    [Google Scholar]
  11. Fournier PE, Dubourg G, Raoult D. Clinical detection and characterization of bacterial pathogens in the genomics era. Genome Med 2014; 6:114 [View Article]
    [Google Scholar]
  12. Rosenberg E. The diversity of bacterial pathogenicity mechanisms. Genome Biol 2005; 6:320 [View Article]
    [Google Scholar]
  13. Johnson M, Zaretskaya I, Raytselis Y, Merezhuk Y, McGinnis S et al. NCBI blast: a better web interface. Nucleic Acids Res 2008; 36:W5–W9 [View Article]
    [Google Scholar]
  14. Edgar RC. Muscle: multiple sequence alignment with high accuracy and high throughput. Nucleic Acids Res 2004; 32:1792–1797 [View Article]
    [Google Scholar]
  15. UniProt Consortium UniProt: a worldwide hub of protein knowledge. Nucleic Acids Res 2019; 47:D506–D515 [View Article]
    [Google Scholar]
  16. Jones P, Binns D, Chang HY, Fraser M, Li W et al. InterProScan 5: genome-scale protein function classification. Bioinformatics 2014; 30:1236–1240 [View Article]
    [Google Scholar]
  17. Waterhouse AM, Procter JB, Martin DMA, Clamp M, Barton GJ. Jalview Version 2–a multiple sequence alignment editor and analysis workbench. Bioinformatics 2009; 25:1189–1191 [View Article]
    [Google Scholar]
  18. Son MS, Matthews WJ Jr, Kang Y, Nguyen DT, Hoang TT. In vivo evidence of Pseudomonas aeruginosa nutrient acquisition and pathogenesis in the lungs of cystic fibrosis patients. Infect Immun 2007; 75:5313–5324 [View Article]
    [Google Scholar]
  19. Rice LB. Federal funding for the study of antimicrobial resistance in nosocomial pathogens: no ESKAPE. J Infect Dis 2008; 197:1079–1081 [View Article]
    [Google Scholar]
  20. Winsor GL, Griffiths EJ, Lo R, Dhillon BK, Shay JA et al. Enhanced annotations and features for comparing thousands of Pseudomonas genomes in the Pseudomonas genome database. Nucleic Acids Res 2016; 44:D646–D653 [View Article]
    [Google Scholar]
  21. Fulton DL, Li YY, Laird MR, Horsman BGS, Roche FM et al. Improving the specificity of high-throughput ortholog prediction. BMC Bioinformatics 2006; 7:270 [View Article]
    [Google Scholar]
  22. Babrowski T, Holbrook C, Moss J, Gottlieb L, Valuckaite V et al. Pseudomonas aeruginosa virulence expression is directly activated by morphine and is capable of causing lethal gut-derived sepsis in mice during chronic morphine administration. Ann Surg 2012; 255:386–393 [View Article]
    [Google Scholar]
  23. Zaborin A, Gerdes S, Holbrook C, Liu DC, Zaborina OY et al. Pseudomonas aeruginosa overrides the virulence inducing effect of opioids when it senses an abundance of phosphate. PLoS One 2012; 7:e34883 [View Article]
    [Google Scholar]
  24. Zaborina O, Lepine F, Xiao G, Valuckaite V, Chen Y et al. Dynorphin activates quorum sensing quinolone signaling in Pseudomonas aeruginosa. PLoS Pathog 2007; 3:e35 [View Article]
    [Google Scholar]
  25. Breslow JM, Monroy MA, Daly JM, Meissler JJ, Gaughan J et al. Morphine, but not trauma, sensitizes to systemic Acinetobacter baumannii infection. J Neuroimmune Pharmacol 2011; 6:551–565 [View Article]
    [Google Scholar]
  26. Shakhsheer BA, Versten LA, Luo JN, Defazio JR, Klabbers R et al. Morphine promotes colonization of anastomotic tissues with collagenase - producing Enterococcus faecalis and causes leak. J Gastrointest Surg 2016; 20:1744–1751 [View Article]
    [Google Scholar]
  27. Glattard E, Welters ID, Lavaux T, Muller AH, Laux A et al. Endogenous morphine levels are increased in sepsis: a partial implication of neutrophils. PLoS One 2010; 5:e8791 [View Article]
    [Google Scholar]
  28. Long MT, Hailes AM, Kirby GW, Bruce NC. Transformations of morphine alkaloids by Pseudomonas putida M10. Appl Environ Microbiol 1995; 61:3645–3649
    [Google Scholar]
  29. Galanie S, Thodey K, Trenchard IJ, Filsinger Interrante M, Smolke CD. Complete biosynthesis of opioids in yeast. Science 2015; 349:1095–1100 [View Article]
    [Google Scholar]
  30. He J, Baldini RL, Déziel E, Saucier M, Zhang Q et al. The broad host range pathogen Pseudomonas aeruginosa strain PA14 carries two pathogenicity islands harboring plant and animal virulence genes. Proc Natl Acad Sci USA 2004; 101:2530–2535 [View Article]
    [Google Scholar]
  31. Strateva T, Yordanov D. Pseudomonas aeruginosa - a phenomenon of bacterial resistance. J Med Microbiol 2009; 58:1133–1148 [View Article]
    [Google Scholar]
  32. Boettcher C, Fellermeier M, Boettcher C, Dräger B, Zenk MH. How human neuroblastoma cells make morphine. Proc Natl Acad Sci USA 2005; 102:8495–8500 [View Article]
    [Google Scholar]
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