{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T22:39:02Z","timestamp":1778625542659,"version":"3.51.4"},"reference-count":34,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2018,3,1]],"date-time":"2018-03-01T00:00:00Z","timestamp":1519862400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["1R01AI116119"],"award-info":[{"award-number":["1R01AI116119"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Appl Environ Microbiol"],"published-print":{"date-parts":[[2018,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            <jats:named-content content-type=\"genus-species\">Salmonella enterica<\/jats:named-content>\n            serovar Typhimurium is the only organism demonstrated to utilize fructose-asparagine (F-Asn) as a source of carbon and nitrogen. In this report, we first used a bioinformatics approach to identify other microorganisms that encode homologs of the\n            <jats:named-content content-type=\"genus-species\">Salmonella<\/jats:named-content>\n            F-Asn utilization enzymes FraB (deglycase), FraD (kinase), and FraE (asparaginase). These candidate organisms were then tested with up to four different methods to confirm their ability to utilize F-Asn. The easiest and most broadly applicable method utilized a biological toxicity assay, which is based on the observation that F-Asn is toxic to a\n            <jats:named-content content-type=\"genus-species\">Salmonella fraB<\/jats:named-content>\n            mutant. Candidate organisms were grown in a rich medium containing F-Asn, and depletion of F-Asn from the medium was inferred by the growth of a\n            <jats:named-content content-type=\"genus-species\">Salmonella fraB<\/jats:named-content>\n            mutant in that same medium. For select organisms, the toxicity assay was cross-validated by direct mass spectrometry-aided measurement of F-Asn in the spent-culture media and through demonstration of FraB and FraD enzyme activity in cellular extracts. For prototrophs, F-Asn utilization was additionally confirmed by growth in a minimal medium containing F-Asn as the sole carbon source. Collectively, these studies established that\n            <jats:named-content content-type=\"genus-species\">Clostridium<\/jats:named-content>\n            <jats:named-content content-type=\"genus-species\">bolteae<\/jats:named-content>\n            ,\n            <jats:named-content content-type=\"genus-species\">Clostridium acetobutylicum<\/jats:named-content>\n            , and\n            <jats:named-content content-type=\"genus-species\">Clostridium clostridioforme<\/jats:named-content>\n            can utilize F-Asn, but\n            <jats:named-content content-type=\"genus-species\">Clostridium difficile<\/jats:named-content>\n            cannot;\n            <jats:named-content content-type=\"genus-species\">Klebsiella oxytoca<\/jats:named-content>\n            and some\n            <jats:named-content content-type=\"genus-species\">Klebsiella pneumoniae<\/jats:named-content>\n            subspecies can utilize F-Asn; and some\n            <jats:named-content content-type=\"genus-species\">Citrobacter rodentium<\/jats:named-content>\n            and\n            <jats:named-content content-type=\"genus-species\">Citrobacter freundii<\/jats:named-content>\n            strains can also utilize F-Asn. Within\n            <jats:named-content content-type=\"genus-species\">Salmonella enterica<\/jats:named-content>\n            , the host-adapted serovars Typhi and Paratyphi A have lost the ability to utilize F-Asn.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            Fructose-asparagine (F-Asn) is a precursor to acrylamide that is found in human foods, and it is also a nutrient source for\n            <jats:named-content content-type=\"genus-species\">Salmonella enterica<\/jats:named-content>\n            , a foodborne pathogen. Here, we determined that among the normal intestinal microbiota, there are species of\n            <jats:named-content content-type=\"genus-species\">Clostridium<\/jats:named-content>\n            that encode the enzymes required for F-Asn utilization. Using complementary experimental approaches, we have confirmed that three members of\n            <jats:named-content content-type=\"genus-species\">Clostridium<\/jats:named-content>\n            , two members of\n            <jats:named-content content-type=\"genus-species\">Klebsiella<\/jats:named-content>\n            , and two members of\n            <jats:named-content content-type=\"genus-species\">Citrobacter<\/jats:named-content>\n            can indeed utilize F-Asn. The\n            <jats:named-content content-type=\"genus-species\">Clostridium<\/jats:named-content>\n            spp. likely compete with\n            <jats:named-content content-type=\"genus-species\">Salmonella<\/jats:named-content>\n            for F-Asn in the gut and contribute to competitive exclusion. FraB, one of the enzymes in the F-Asn utilization pathway, is a potential drug target because inhibition of this enzyme leads to the accumulation of a toxic metabolite that inhibits the growth of\n            <jats:named-content content-type=\"genus-species\">Salmonella<\/jats:named-content>\n            species. This study identifies the potential off-target organisms that need to be considered when developing therapeutics directed at FraB.\n          <\/jats:p>","DOI":"10.1128\/aem.01957-17","type":"journal-article","created":{"date-parts":[[2017,12,19]],"date-time":"2017-12-19T13:37:08Z","timestamp":1513690628000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":23,"title":["Identification of Bacterial Species That Can Utilize Fructose-Asparagine"],"prefix":"10.1128","volume":"84","author":[{"given":"Anice","family":"Sabag-Daigle","sequence":"first","affiliation":[{"name":"Department of Microbial Infection and Immunity, The Ohio State University, Columbus, Ohio, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jikang","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, The Ohio State University, Columbus, Ohio, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mikayla A.","family":"Borton","sequence":"additional","affiliation":[{"name":"Department of Microbiology, The Ohio State University, Columbus, Ohio, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anindita","family":"Sengupta","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, The Ohio State University, Columbus, Ohio, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Venkat","family":"Gopalan","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, The Ohio State University, Columbus, Ohio, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kelly C.","family":"Wrighton","sequence":"additional","affiliation":[{"name":"Department of Microbiology, The Ohio State University, Columbus, Ohio, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vicki H.","family":"Wysocki","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, The Ohio State University, Columbus, Ohio, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian M. 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