{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T19:54:00Z","timestamp":1777060440789,"version":"3.51.4"},"reference-count":44,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2015,10,1]],"date-time":"2015-10-01T00:00:00Z","timestamp":1443657600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2015,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Because a shortage of new antimicrobial agents is a critical issue at present, and with the spread of multidrug-resistant (MDR) pathogens, the use of fosfomycin to treat infections is being revisited as a \u201clast-resort option.\u201d This drug offers a particular benefit in that it is more effective against bacteria growing under oxygen-limited conditions, unlike other commonly used antimicrobials, such as fluoroquinolones and aminoglycosides. In this study, we showed that\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Escherichia coli<\/jats:named-content>\n            strains, including enterohemorrhagic\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">E. coli<\/jats:named-content>\n            (EHEC), were more susceptible to fosfomycin when grown anaerobically than when grown aerobically, and we investigated how the activity of this drug was enhanced during anaerobic growth of\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">E. coli<\/jats:named-content>\n            . Our quantitative PCR analysis and a transport assay showed that\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">E. coli<\/jats:named-content>\n            cells grown under anaerobic conditions had higher levels of expression of\n            <jats:italic>glpT<\/jats:italic>\n            and\n            <jats:italic>uhpT<\/jats:italic>\n            , encoding proteins that transport fosfomycin into cells with their native substrates, i.e., glycerol-3-phosphate and glucose-6-phosphate, and led to increased intracellular accumulation of the drug. Elevation of expression of these genes during anaerobic growth requires FNR, a global transcriptional regulator that is activated under anaerobic conditions. Purified FNR bound to DNA fragments from regions upstream of\n            <jats:italic>glpT<\/jats:italic>\n            and\n            <jats:italic>uhpT<\/jats:italic>\n            , suggesting that it is an activator of expression of\n            <jats:italic>glpT<\/jats:italic>\n            and\n            <jats:italic>uhpT<\/jats:italic>\n            during anaerobic growth. We concluded that the increased antibacterial activity of fosfomycin toward\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">E. coli<\/jats:named-content>\n            under anaerobic conditions can be attributed to elevated expression of GlpT and UhpT following activation of FNR, leading to increased uptake of the drug.\n          <\/jats:p>","DOI":"10.1128\/aac.01176-15","type":"journal-article","created":{"date-parts":[[2015,7,28]],"date-time":"2015-07-28T01:31:15Z","timestamp":1438047075000},"page":"6352-6360","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":23,"title":["Elevated Expression of GlpT and UhpT via FNR Activation Contributes to Increased Fosfomycin Susceptibility in Escherichia coli under Anaerobic Conditions"],"prefix":"10.1128","volume":"59","author":[{"given":"Kumiko","family":"Kurabayashi","sequence":"first","affiliation":[{"name":"Advanced Scientific Research Leaders Development Unit, Gunma University, Graduate School of Medicine, Gunma, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Koichi","family":"Tanimoto","sequence":"additional","affiliation":[{"name":"Laboratory of Bacterial Drug Resistance, Gunma University, Graduate School of Medicine, Gunma, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shinobu","family":"Fueki","sequence":"additional","affiliation":[{"name":"Advanced Scientific Research Leaders Development Unit, Gunma University, Graduate School of Medicine, Gunma, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haruyoshi","family":"Tomita","sequence":"additional","affiliation":[{"name":"Department of Bacteriology, Gunma University, Graduate School of Medicine, Gunma, Japan"},{"name":"Laboratory of Bacterial Drug Resistance, Gunma University, Graduate School of Medicine, Gunma, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hidetada","family":"Hirakawa","sequence":"additional","affiliation":[{"name":"Advanced Scientific Research Leaders Development Unit, Gunma University, Graduate School of Medicine, Gunma, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","first-page":"43","article-title":"The importance of oxygen in the killing of bacteria by ofloxacin and ciprofloxacin","volume":"79","author":"Morrissey I","year":"1994","unstructured":"Morrissey I, Smith JT. 1994. 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