title: A link between gut community metabolism and pathogenesis: molecular hydrogen-stimulated glucarate catabolism aids Salmonella virulence.
abstract: Glucarate, an oxidized product of glucose, is a major serum organic acid in humans. Still, its role as a carbon source for a pathogen colonizing hosts has not been studied. We detected high-level expression of a potential glucarate permease encoding gene gudT when Salmonella enterica serovar Typhimurium are exposed to hydrogen gas (H(2)), a gaseous by-product of gut commensal metabolism. A gudT strain of Salmonella is deficient in glucarate-dependent growth, however, it can still use other monosaccharides, such as glucose or galactose. Complementation of the gudT mutant with a plasmid harbouring gudT restored glucarate-dependent growth to wild-type (WT) levels. The gudT mutant exhibits attenuated virulence: the mean time of death for mice inoculated with WT strain was 2 days earlier than for mice inoculated with the gudT strain. At 4 days postinoculation, liver and spleen homogenates from mice inoculated with a gudT strain contained significantly fewer viable Salmonella than homogenates from animals inoculated with the parent. The parent strain grew well H(2)-dependently in a minimal medium with amino acids and glucarate provided as the sole carbon sources, whereas the gudT strain achieved approximately 30% of the parent strain's yield. Glucarate-mediated growth of a mutant strain unable to produce H(2) was stimulated by H(2) addition, presumably owing to the positive transcriptional response to H(2). Gut microbiota-produced molecular hydrogen apparently signals Salmonella to catabolize an alternative carbon source available in the host. Our results link a gut microbiome-produced diffusible metabolite to augmenting bacterial pathogenesis.
authors.affiliation: Department of Microbiology, University of Georgia, Athens, Georgia.
authors.forename: Reena
authors.initials: R
authors.lastname: Lamichhane-Khadka
authors.forename: Stéphane L
authors.initials: SL
authors.lastname: Benoit
authors.forename: Susan E
authors.initials: SE
authors.lastname: Maier
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Maier
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D005977:Glutarates / Q000378:metabolism*; D006859:Hydrogen / Q000378:metabolism*; D008099:Liver / Q000382:microbiology; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D012481:Salmonella Infections, Animal / Q000382:microbiology* / Q000473:pathology; D012486:Salmonella typhimurium / Q000235:genetics / Q000254:growth & development / Q000378:metabolism* / Q000472:pathogenicity*; D013154:Spleen / Q000382:microbiology; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D005977:Glutarates; D026901:Membrane Transport Proteins; D037521:Virulence Factors; D006859:Hydrogen
keywords: carbon transport; gut microbiome; in vivo pathogen growth; metabolism and virulence; microbial carbon utilization