{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Sabag-Daigle A"],"funding":["NIAID NIH HHS"],"pagination":["28117"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC4941530"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["6"],"pubmed_abstract":["Insertions in the Salmonella enterica fra locus, which encodes the fructose-asparagine (F-Asn) utilization pathway, are highly attenuated in 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 to the wild-type or a fra island deletion mutant. We hypothesized that the presence of FraD kinase and absence of FraB deglycase causes build-up of a toxic metabolite: 6-phosphofructose-aspartate (6-P-F-Asp). We used biochemical assays to assess FraB and FraD activities, and mass spectrometry to confirm that the fraB mutant accumulates 6-P-F-Asp. These results, together with our finding that mutants lacking fraD or the fra island are not attenuated in mice, suggest that the extreme attenuation of a fraB mutant stems from 6-P-F-Asp toxicity. Salmonella FraB is therefore an excellent drug target, a prospect strengthened by the absence of the fra locus in most of the gut microbiota."],"journal":["Scientific reports"],"pubmed_title":["A metabolic intermediate of the fructose-asparagine utilization pathway inhibits growth of a Salmonella fraB mutant."],"pmcid":["PMC4941530"],"funding_grant_id":["R01 AI116119"],"pubmed_authors":["Ahmer BM","Wu J","Behrman EJ","Bogard AJ","Wysocki VH","Stahl C","Blunk HM","Sabag-Daigle A","Gopalan V","Sengupta A","Ali MM"],"additional_accession":[]},"is_claimable":false,"name":"A metabolic intermediate of the fructose-asparagine utilization pathway inhibits growth of a Salmonella fraB mutant.","description":"Insertions in the Salmonella enterica fra locus, which encodes the fructose-asparagine (F-Asn) utilization pathway, are highly attenuated in 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 to the wild-type or a fra island deletion mutant. We hypothesized that the presence of FraD kinase and absence of FraB deglycase causes build-up of a toxic metabolite: 6-phosphofructose-aspartate (6-P-F-Asp). We used biochemical assays to assess FraB and FraD activities, and mass spectrometry to confirm that the fraB mutant accumulates 6-P-F-Asp. These results, together with our finding that mutants lacking fraD or the fra island are not attenuated in mice, suggest that the extreme attenuation of a fraB mutant stems from 6-P-F-Asp toxicity. Salmonella FraB is therefore an excellent drug target, a prospect strengthened by the absence of the fra locus in most of the gut microbiota.","dates":{"release":"2016-01-01T00:00:00Z","publication":"2016 Jul","modification":"2026-05-05T15:19:50.262Z","creation":"2019-03-27T02:18:10Z"},"accession":"S-EPMC4941530","cross_references":{"pubmed":["27403719"],"doi":["10.1038/srep28117"]}}