期刊
OPEN BIOLOGY
卷 3, 期 12, 页码 -出版社
ROYAL SOC
DOI: 10.1098/rsob.130146
关键词
microbial carbon utilization; carbon transport; in vivo pathogen growth; gut microbiome; metabolism and virulence
资金
- National Institutes of Health [1R21AI073322]
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 post-inoculation, 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.
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