Alternative spermidine biosynthetic route is critical for growth of Campylobacter jejuni and is the dominant polyamine pathway in human gut microbiota

Colin C. Hanfrey, Bruce M. Pearson, Stuart Hazeldine, Jeongmi Lee, Duncan J. Gaskin, Patrick M. Woster, Margaret A. Phillips, Anthony J. Michael

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

The availability of fully sequenced bacterial genomes has revealed that many species known to synthesize the polyamine spermidine lack the spermidine biosynthetic enzymes S-adenosylmethionine decarboxylase and spermidine synthase. We found that such species possess orthologues of the sym-norspermidine biosynthetic enzymes carboxynorspermidine dehydrogenase and carboxynorspermidine decarboxylase. By deleting these genes in the food-borne pathogen Campylobacter jejuni, we found that the carboxynorspermidine decarboxylase orthologue is responsible for synthesizing spermidine and not sym-norspermidine in vivo. In polyamine auxotrophic gene deletion strains of C. jejuni, growth is highly compromised but can be restored by exogenous sym-homospermidine and to a lesser extent by sym-norspermidine. The alternative spermidine biosynthetic pathway is present in many bacterial phyla and is the dominant spermidine route in the human gut, stomach, and oral microbiomes, and it appears to have supplanted the S-adenosylmethionine decarboxylase/spermidine synthase pathway in the gut microbiota. Approximately half of the gut Firmicutes species appear to be polyamine auxotrophs, but all encode the potA-BCD spermidine/putrescine transporter. Orthologues encoding carboxyspermidine dehydrogenase and carboxyspermidine decarboxylase are found clustered with an array of diverse putrescine biosynthetic genes in different bacterial genomes, consistent with a role in spermidine, rather than sym-norspermidine biosynthesis. Due to the pervasiveness of ε-proteobacteria in deep sea hydrothermal vents and to the ubiquity of the alternative spermidine biosynthetic pathway in that phylum, the carboxyspermidine route is also dominant in deep sea hydrothermal vents. The carboxyspermidine pathway for polyamine biosynthesis is found in diverse human pathogens, and this alternative spermidine biosynthetic route presents an attractive target for developing novel antimicrobial compounds.

Original languageEnglish (US)
Pages (from-to)43301-43312
Number of pages12
JournalJournal of Biological Chemistry
Volume286
Issue number50
DOIs
StatePublished - Dec 16 2011

Fingerprint

Campylobacter jejuni
Spermidine
Polyamines
Hydrothermal Vents
Growth
Genes
Spermidine Synthase
Adenosylmethionine Decarboxylase
Bacterial Genomes
Putrescine
Vents
Biosynthesis
Biosynthetic Pathways
Pathogens
Oxidoreductases
Gastrointestinal Microbiome
Proteobacteria
Carboxy-Lyases
Microbiota
Gene Deletion

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Alternative spermidine biosynthetic route is critical for growth of Campylobacter jejuni and is the dominant polyamine pathway in human gut microbiota. / Hanfrey, Colin C.; Pearson, Bruce M.; Hazeldine, Stuart; Lee, Jeongmi; Gaskin, Duncan J.; Woster, Patrick M.; Phillips, Margaret A.; Michael, Anthony J.

In: Journal of Biological Chemistry, Vol. 286, No. 50, 16.12.2011, p. 43301-43312.

Research output: Contribution to journalArticle

Hanfrey, Colin C. ; Pearson, Bruce M. ; Hazeldine, Stuart ; Lee, Jeongmi ; Gaskin, Duncan J. ; Woster, Patrick M. ; Phillips, Margaret A. ; Michael, Anthony J. / Alternative spermidine biosynthetic route is critical for growth of Campylobacter jejuni and is the dominant polyamine pathway in human gut microbiota. In: Journal of Biological Chemistry. 2011 ; Vol. 286, No. 50. pp. 43301-43312.
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