Abstract
Salmonella enterica serovar Typhimurium (Salmonella) is one of the most significant food-borne pathogens affecting both humans and agriculture. We have determined that Salmonella encodes an uptake and utilization pathway specific for a novel nutrient, fructose-asparagine (F-Asn), which is essential for Salmonella fitness in the inflamed intestine (modeled using germ-free, streptomycin-treated, ex-germ-free with human microbiota, and IL10-/- mice). The locus encoding F-Asn utilization, fra, provides an advantage only if Salmonella can initiate inflammation and use tetrathionate as a terminal electron acceptor for anaerobic respiration (the fra phenotype is lost in Salmonella SPI1- SPI2- or ttrA mutants, respectively). The severe fitness defect of a Salmonella fra mutant suggests that F-Asn is the primary nutrient utilized by Salmonella in the inflamed intestine and that this system provides a valuable target for novel therapies.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Anaerobiosis
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Animals
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Asparagine / metabolism*
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Bacterial Proteins / genetics
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Biological Transport / genetics
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Cation Transport Proteins / genetics
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Disease Models, Animal
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Energy Metabolism / genetics
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Fructose / metabolism*
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Humans
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Inflammation / immunology
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Inflammation / microbiology
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Interleukin-10 / genetics
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Intestinal Mucosa / metabolism*
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Intestines / immunology
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Intestines / microbiology
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Membrane Proteins / genetics
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Mice, Knockout
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Salmonella Infections / metabolism*
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Salmonella Infections, Animal / genetics
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Salmonella typhimurium / genetics
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Salmonella typhimurium / growth & development
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Salmonella typhimurium / metabolism*
Substances
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Bacterial Proteins
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Cation Transport Proteins
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IL10 protein, mouse
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Membrane Proteins
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SPI-2 protein, Salmonella
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Spi1 protein, Salmonella
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natural resistance-associated macrophage protein 1
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Interleukin-10
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Fructose
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Asparagine