A metabolic intermediate of the fructose-asparagine utilization pathway inhibits growth of a Salmonella fraB mutant.

摘要: Insertions in the Salmonella enterica fra locus, which encodes fructose-asparagine (F-Asn) utilization pathway, are highly attenuated mouse models of inflammation (>1000-fold competitive index). Here, we report that F-Asn is bacteriostatic to a fraB mutant (IC50 19 μM), but not wild-type or island deletion mutant. We hypothesized presence FraD kinase and absence FraB deglycase causes build-up toxic metabolite: 6-phosphofructose-aspartate (6-P-F-Asp). used biochemical assays assess activities, mass spectrometry confirm accumulates 6-P-F-Asp. These results, together with our finding mutants lacking fraD mice, suggest extreme attenuation stems from 6-P-F-Asp toxicity. therefore an excellent drug target, prospect strengthened by locus most gut microbiota.