{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T16:02:12Z","timestamp":1753891332180,"version":"3.41.2"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,5,6]],"date-time":"2022-05-06T00:00:00Z","timestamp":1651795200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"JSPS","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p>Enterohemorrhagic <jats:italic>Escherichia coli<\/jats:italic> (EHEC) is one of the most common foodborne pathogens. However, no drug that prevents the severe complications caused by this bacterium has been approved yet. This study showed that a macroporous magnesium oxide (MgO)-templated carbon material (MgOC<jats:sub>150<\/jats:sub>) adsorbs Shiga toxins, and Type III secretory EspA\/EspB proteins responsible for EHEC pathogenesis, and decreases the extracellular levels of these proteins. On the other hand, this material did not affect the growth of EHEC. <jats:italic>Citrobacter rodentium<\/jats:italic> traditionally used to estimate Type III secretion system-associated virulence in mice is highly virulent. The survival period of infected mice was prolonged when MgOC<jats:sub>150<\/jats:sub> was administered. This adsorbent disturbed neither mammalian cells nor normal intestinal bacteria, such as <jats:italic>Enterococcus hirae<\/jats:italic>, <jats:italic>Lactobacillus acidophilus<\/jats:italic>, and <jats:italic>Lactobacillus casei<\/jats:italic>. In contrast, MgOC<jats:sub>150<\/jats:sub> adsorbed antimicrobial agents, including \u03b2-lactams, quinolones, tetracyclines, and trimethoprim\/sulfamethoxazole. However, fosfomycin and amikacin were not adsorbed. Thus, MgOC<jats:sub>150<\/jats:sub> can be used with fosfomycin and amikacin to treat infections. MgOC<jats:sub>150<\/jats:sub> is used for industrial purposes, such as an electrode catalyst, a bioelectrode, and enzyme immobilization. The study proposed another potential application of MgOC<jats:sub>150<\/jats:sub>, assisting anti-EHEC chemotherapy.<\/jats:p>","DOI":"10.3389\/fmicb.2022.883689","type":"journal-article","created":{"date-parts":[[2022,5,6]],"date-time":"2022-05-06T04:48:52Z","timestamp":1651812532000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["A Macroporous Magnesium Oxide-Templated Carbon Adsorbs Shiga Toxins and Type III Secretory Proteins in Enterohemorrhagic Escherichia coli, Which Attenuates Virulence"],"prefix":"10.3389","volume":"13","author":[{"given":"Hidetada","family":"Hirakawa","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazutomo","family":"Suzue","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Motoyuki","family":"Uchida","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayako","family":"Takita","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wataru","family":"Kamitani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haruyoshi","family":"Tomita","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,5,6]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1038\/nrmicro2265","article-title":"Molecular mechanisms of Escherichia coli pathogenicity","volume":"8","author":"Croxen","year":"2010","journal-title":"Nat. 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Microbiol."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"351","DOI":"10.7861\/clinmedicine.15-4-351","article-title":"Drug treatment of pruritus in liver diseases","volume":"15","author":"Hegade","year":"2015","journal-title":"Clin. Med."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1099\/mic.0.020420-0","article-title":"Secreted indole serves as a signal for expression of type III secretion system translocators in enterohaemorrhagic Escherichia coli O157:H7","volume":"155","author":"Hirakawa","year":"2009","journal-title":"Microbiology"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"15173","DOI":"10.1038\/s41598-020-72412-w","article-title":"Roles of the Tol-Pal system in the type III secretion system and flagella-mediated virulence in enterohemorrhagic Escherichia coli","volume":"10","author":"Hirakawa","year":"","journal-title":"Sci. Rep."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"434","DOI":"10.3390\/antibiotics10040434","article-title":"Adsorption of phenazines produced by pseudomonas aeruginosa using AST-120 decreases pyocyanin-associated cytotoxicity","volume":"10","author":"Hirakawa","year":"2021","journal-title":"Antibiotics"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"e0232461","DOI":"10.1371\/journal.pone.0232461","article-title":"In vitro activity of AST-120 that suppresses indole signaling in Escherichia coli, which attenuates drug tolerance and virulence","volume":"15","author":"Hirakawa","year":"","journal-title":"PLoS One"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"669","DOI":"10.1046\/j.1462-5822.2001.00146.x","article-title":"Characterization of translocation pores inserted into plasma membranes by type III-secreted Esp proteins of enteropathogenic Escherichia coli","volume":"3","author":"Ide","year":"2001","journal-title":"Cell. Microbiol."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1016\/j.chom.2007.09.012","article-title":"The enteropathogenic E. coli effector EspB facilitates microvillus effacing and antiphagocytosis by inhibiting myosin function","volume":"2","author":"Iizumi","year":"2007","journal-title":"Cell Host Microbe"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"3153","DOI":"10.1016\/j.carbon.2004.07.029","article-title":"Pore structure of carbons coated on ceramic particles","volume":"42","author":"Inagaki","year":"2004","journal-title":"Carbon"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1016\/S0092-8674(00)80437-7","article-title":"Enteropathogenic E. coli (EPEC) transfers its receptor for intimate adherence into mammalian cells","volume":"91","author":"Kenny","year":"1997","journal-title":"Cell"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1086\/515592","article-title":"Induction of apoptosis in normal human renal tubular epithelial cells by Escherichia coli Shiga toxins 1 and 2","volume":"178","author":"Kiyokawa","year":"1998","journal-title":"J. Infect. Dis."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1046\/j.1462-5822.2002.00176.x","article-title":"The EspB protein of enterohaemorrhagic Escherichia coli interacts directly with alpha-catenin","volume":"4","author":"Kodama","year":"2002","journal-title":"Cell. Microbiol."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"775","DOI":"10.1128\/iai.18.3.775-779.1977","article-title":"Vero response to a cytotoxin of Escherichia coli","volume":"18","author":"Konowalchuk","year":"1977","journal-title":"Infect. Immun."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"27505","DOI":"10.1074\/jbc.M113.462622","article-title":"Structural basis of subtilase cytotoxin SubAB assembly","volume":"288","author":"Le Nours","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"8834","DOI":"10.1016\/S0021-9258(18)47490-X","article-title":"Glycolipid binding of purified and recombinant Escherichia coli produced verotoxin in vitro","volume":"262","author":"Lingwood","year":"1987","journal-title":"J. Biol. Chem."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1089\/fpd.2013.1704","article-title":"Global incidence of human Shiga toxin-producing Escherichia coli infections and deaths: a systematic review and knowledge synthesis","volume":"11","author":"Majowicz","year":"2014","journal-title":"Foodborne Pathog. Dis."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1016\/j.jelechem.2017.12.041","article-title":"Pore size effect of MgO-templated carbon on enzymatic H-2 oxidation by the hyperthermophilic hydrogenase from Aquifex aeolicus","volume":"812","author":"Mazurenko","year":"2018","journal-title":"J. Electroanal. 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Microbiol."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1292\/jvms.63.281","article-title":"Adsorption effect of activated charcoal on enterohemorrhagic Escherichia coli","volume":"63","author":"Naka","year":"2001","journal-title":"J. Vet. Med. Sci."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"15571","DOI":"10.1038\/s41598-019-51292-9","article-title":"AST-120, an oral carbon absorbent, protects against the progression of atherosclerosis in a mouse chronic renal failure model by preserving sFlt-1 expression levels","volume":"9","author":"Nakada","year":"2019","journal-title":"Sci. Rep."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"5717","DOI":"10.1128\/IAI.67.11.5717-5722.1999","article-title":"Monoclonal antibody to Shiga toxin 2 which blocks receptor binding and neutralizes cytotoxicity","volume":"67","author":"Nakao","year":"1999","journal-title":"Infect. Immun."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1128\/CMR.11.1.142","article-title":"Diarrheagenic Escherichia coli","volume":"11","author":"Nataro","year":"1998","journal-title":"Clin. Microbiol. Rev."},{"key":"ref28","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1111\/j.1744-9987.2010.00882.x","article-title":"Role of indoxyl sulfate in the progression of chronic kidney disease and cardiovascular disease: experimental and clinical effects of oral sorbent AST-120","volume":"15","author":"Niwa","year":"2011","journal-title":"Ther. Apher. 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Med."},{"key":"ref35","doi-asserted-by":"publisher","first-page":"310","DOI":"10.5483\/BMBRep.2009.42.5.310","article-title":"Globotriaosylceramide (Gb3) content in HeLa cells is correlated to Shiga toxin-induced cytotoxicity and Gb3 synthase expression","volume":"42","author":"Shin","year":"2009","journal-title":"BMB Rep."},{"key":"ref36","doi-asserted-by":"publisher","first-page":"1073","DOI":"10.1016\/S0140-6736(05)71144-2","article-title":"Shiga-toxin-producing Escherichia coli and haemolytic uraemic syndrome","volume":"365","author":"Tarr","year":"2005","journal-title":"Lancet"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1128\/IAI.67.1.120-125.1999","article-title":"Expression of the EspB protein of enteropathogenic Escherichia coli within HeLa cells affects stress fibers and cellular morphology","volume":"67","author":"Taylor","year":"1999","journal-title":"Infect. Immun."},{"key":"ref38","doi-asserted-by":"publisher","first-page":"1337","DOI":"10.1001\/jama.290.10.1337","article-title":"Effect of an oral Shiga toxin-binding agent on diarrhea-associated hemolytic uremic syndrome in children: a randomized controlled trial","volume":"290","author":"Trachtman","year":"2003","journal-title":"JAMA"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"14432","DOI":"10.1021\/ja5053736","article-title":"Exceptionally high glucose current on a hierarchically structured porous carbon electrode with \u201cwired\u201d Flavin adenine dinucleotide-dependent glucose dehydrogenase","volume":"136","author":"Tsujimura","year":"2014","journal-title":"J. Am. Chem. Soc."},{"key":"ref40","doi-asserted-by":"publisher","first-page":"753","DOI":"10.1046\/j.1462-5822.2001.00159.x","article-title":"Role of EscF, a putative needle complex protein, in the type III protein translocation system of enteropathogenic Escherichia coli","volume":"3","author":"Wilson","year":"2001","journal-title":"Cell. Microbiol."},{"key":"ref41","doi-asserted-by":"publisher","first-page":"1930","DOI":"10.1056\/NEJM200006293422601","article-title":"The risk of the hemolytic-uremic syndrome after antibiotic treatment of Escherichia coli O157:H7 infections","volume":"342","author":"Wong","year":"2000","journal-title":"N. Engl. J. Med."},{"key":"ref42","doi-asserted-by":"publisher","first-page":"738","DOI":"10.1086\/323082","article-title":"Efficacy of postinfection treatment with anti-Shiga toxin (Stx) 2 humanized monoclonal antibody TMA-15 in mice lethally challenged with Stx-producing Escherichia coli","volume":"184","author":"Yamagami","year":"2001","journal-title":"J. Infect. Dis."},{"key":"ref43","doi-asserted-by":"publisher","first-page":"2739","DOI":"10.1016\/j.lfs.2003.10.022","article-title":"Effects of the dietary supplements, activated charcoal and copper chlorophyllin, on urinary excretion of trimethylamine in Japanese trimethylaminuria patients","volume":"74","author":"Yamazaki","year":"2004","journal-title":"Life Sci."},{"key":"ref44","doi-asserted-by":"publisher","first-page":"2667","DOI":"10.1182\/blood-2016-10-744060","article-title":"Indoxyl sulfate induces platelet hyperactivity and contributes to chronic kidney disease-associated thrombosis in mice","volume":"129","author":"Yang","year":"2017","journal-title":"Blood"},{"key":"ref45","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1038\/nsmb879","article-title":"Structural characterization of a type III secretion system filament protein in complex with its chaperone","volume":"12","author":"Yip","year":"2005","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref46","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/j.clim.2010.09.009","article-title":"Identification of a novel linear epitope on EspA from enterohemorrhagic E. coli using a neutralizing and protective monoclonal antibody","volume":"138","author":"Yu","year":"2011","journal-title":"Clin. Immunol."},{"key":"ref47","doi-asserted-by":"publisher","first-page":"311","DOI":"10.3238\/arztebl.2019.0311","article-title":"The use of activated charcoal to treat intoxications","volume":"116","author":"Zellner","year":"2019","journal-title":"Dtsch. Arztebl. 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