A metabolic intermediate of the fructose-asparagine utilization pathway inhibits growth of a Salmonella fraB mutant.
A metabolic intermediate of the fructose-asparagine utilization pathway inhibits growth of a Salmonella fraB mutant.
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DOI：
10.1038/srep28117
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发表时间：
2016-07-12
影响因子：
4.6
通讯作者：
Ahmer BM
中科院分区：
文献类型：
--
作者：
Sabag-Daigle A;Blunk HM;Sengupta A;Wu J;Bogard AJ;Ali MM;Stahl C;Wysocki VH;Gopalan V;Behrman EJ;Ahmer BM
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.
