title: Polyamines are essential for virulence in Salmonella enterica serovar Gallinarum despite evolutionary decay of polyamine biosynthesis genes.
abstract: Serovars of Salmonella enterica exhibit different host-specificities where some have broad host-ranges and others, like S. Gallinarum and S. Typhi, are host-specific for poultry and humans, respectively. With the recent availability of whole genome sequences it has been reported that host-specificity coincides with accumulation of pseudogenes, indicating adaptation of host-restricted serovars to their narrow niches. Polyamines are small cationic amines and in Salmonella they can be synthesized through two alternative pathways directly from l-ornithine to putrescine and from l-arginine via agmatine to putrescine. The first pathway is not active in S. Gallinarum and S. Typhi, and this prompted us to investigate the importance of polyamines for virulence in S. Gallinarum. Bioinformatic analysis of all sequenced genomes of Salmonella revealed that pseudogene formation of the speC gene was exclusive for S. Typhi and S. Gallinarum and happened through independent events. The remaining polyamine biosynthesis pathway was found to be essential for oral infection with S. Gallinarum since single and double mutants in speB and speE, encoding the pathways from agmatine to putrescine and from putrescine to spermidine, were attenuated. In contrast, speB was dispensable after intraperitoneal challenge, suggesting that putrescine was less important for the systemic phase of the disease. In support of this hypothesis, a ΔspeE;ΔpotCD mutant, unable to synthesize and import spermidine, but with retained ability to import and synthesize putrescine, was attenuated after intraperitoneal infection. We therefore conclude that polyamines are essential for virulence of S. Gallinarum. Furthermore, our results point to distinct roles for putrescine and spermidine during systemic infection.
authors.affiliation: Department of Veterinary Disease Biology, Faculty of Life Sciences, University of Copenhagen, Frederiksberg C, Denmark.
authors.forename: Casper
authors.initials: C
authors.lastname: Schroll
authors.affiliation: Department of Veterinary Disease Biology, Faculty of Life Sciences, University of Copenhagen, Frederiksberg C, Denmark.
authors.forename: Jens P
authors.initials: JP
authors.lastname: Christensen
authors.affiliation: Department of Veterinary Disease Biology, Faculty of Life Sciences, University of Copenhagen, Frederiksberg C, Denmark.
authors.forename: Henrik
authors.initials: H
authors.lastname: Christensen
authors.affiliation: Department of Veterinary Disease Biology, Faculty of Life Sciences, University of Copenhagen, Frederiksberg C, Denmark.
authors.forename: Susanne E
authors.initials: SE
authors.lastname: Pors
authors.affiliation: Department of Veterinary Disease Biology, Faculty of Life Sciences, University of Copenhagen, Frederiksberg C, Denmark.
authors.forename: Lotte
authors.initials: L
authors.lastname: Thorndahl
authors.affiliation: Systems Biotechnology, Department of Systems Biology, Technical University of Denmark, Lyngby, Denmark.
authors.forename: Peter R
authors.initials: PR
authors.lastname: Jensen
authors.affiliation: Department of Veterinary Disease Biology, Faculty of Life Sciences, University of Copenhagen, Frederiksberg C, Denmark.
authors.forename: John E
authors.initials: JE
authors.lastname: Olsen
authors.affiliation: Department of Veterinary Disease Biology, Faculty of Life Sciences, University of Copenhagen, Frederiksberg C, Denmark. Electronic address: loj@sund.ku.dk.
authors.forename: Lotte
authors.initials: L
authors.lastname: Jelsbak
mesh_terms: D000818:Animals; D002460:Cell Line; D002645:Chickens; D019143:Evolution, Molecular; D020868:Gene Silencing; D042541:Intracellular Space / Q000382:microbiology; D008264:Macrophages / Q000382:microbiology; D008297:Male; D050296:Microbial Viability; D009154:Mutation; D011073:Polyamines / Q000378:metabolism*; D011201:Poultry Diseases / Q000382:microbiology* / Q000401:mortality / Q000473:pathology; D011544:Pseudogenes / Q000235:genetics; D012481:Salmonella Infections, Animal / Q000382:microbiology* / Q000401:mortality / Q000473:pathology; D019779:Salmonella enterica / Q000235:genetics* / Q000472:pathogenicity*; D012485:Salmonella typhi / Q000235:genetics / Q000472:pathogenicity; D014774:Virulence / Q000235:genetics*
chemical_list: D011073:Polyamines
keywords: Evolution; Host-specificity; Polyamines; Salmonella Gallinarum; Virulence