{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T04:07:35Z","timestamp":1792123655361,"version":"4.4.0"},"reference-count":29,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T00:00:00Z","timestamp":1747785600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T00:00:00Z","timestamp":1747785600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["22K14892, 24K21872, 24K01760"],"award-info":[{"award-number":["22K14892, 24K21872, 24K01760"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["23K24131"],"award-info":[{"award-number":["23K24131"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["23K06130"],"award-info":[{"award-number":["23K06130"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013171","name":"Ryobi Teien Memory Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013171","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013171","name":"Ryobi Teien Memory Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013171","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007449","name":"Takeda Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007449","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003837","name":"Ichiro Kanehara Foundation for the Promotion of Medical Sciences and Medical Care","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003837","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":[[2025,5,21]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              Colanic acid and enterobacterial common antigen (ECA) are cell-surface polysaccharides that are produced by many\n              <jats:italic toggle=\"yes\">Escherichia coli<\/jats:italic>\n              isolates. Colanic acid is induced under acidic, low temperature, and high-salt conditions and is important for\n              <jats:italic toggle=\"yes\">E. coli<\/jats:italic>\n              resistance to these stresses; however, the role of ECA in these stresses is less clear. Here, we observed that knockout of flippase\n              <jats:italic toggle=\"yes\">wzxE<\/jats:italic>\n              , which translocates lipid-linked ECA repeat units from the cytoplasmic side of the inner membrane to the periplasmic side, resulted in the sensitivity of\n              <jats:italic toggle=\"yes\">E. coli<\/jats:italic>\n              BW25113 to acidic conditions. The\n              <jats:italic toggle=\"yes\">wzxE<\/jats:italic>\n              -knockout mutant showed reduced growth potential and viable counts in vegetable extracts with acidic environments, including cherry tomatoes, carrots, celery, lettuce, and spinach. A double-knockout strain of\n              <jats:italic toggle=\"yes\">wzxE<\/jats:italic>\n              and\n              <jats:italic toggle=\"yes\">wecF<\/jats:italic>\n              (glycosyltransferase that adds the third-and-final sugar of the lipid-linked ECA repeat unit) was not sensitive to acidic conditions, with similar results obtained for a double-knockout strain of\n              <jats:italic toggle=\"yes\">wzxE<\/jats:italic>\n              and\n              <jats:italic toggle=\"yes\">wcaJ<\/jats:italic>\n              (glycosyltransferase that initiates colanic acid lipid-linked repeat-unit biosynthesis). The\n              <jats:italic toggle=\"yes\">wzxE<\/jats:italic>\n              -knockout mutant was sensitive to low temperatures or high-salt conditions, which induced colanic acid synthesis, and these sensitivities were abolished by the additional knockout of\n              <jats:italic toggle=\"yes\">wcaJ<\/jats:italic>\n              . These results suggest that lipid-linked ECA repeat units confer\n              <jats:italic toggle=\"yes\">E. coli<\/jats:italic>\n              susceptibility to acidic, low temperatures, and high-salt conditions in a colanic acid-dependent manner and that\n              <jats:italic toggle=\"yes\">wzxE<\/jats:italic>\n              suppresses this negative effect.\n            <\/jats:p>\n            <jats:sec>\n              <jats:title>IMPORTANCE<\/jats:title>\n              <jats:p>\n                The role of the common enterobacterial antigen, a polysaccharide that is conserved throughout enterobacteria, in stress resistance is unclear. Our results suggest that lipid-linked enterobacterial common antigen repeat units (which are typically translocated across the inner membrane by the flippase WzxE) cause sensitivity of\n                <jats:italic toggle=\"yes\">Escherichia coli<\/jats:italic>\n                to acidic, low-temperature, and high-salt conditions in a manner dependent on colanic acid. The\n                <jats:italic toggle=\"yes\">wzxE<\/jats:italic>\n                -knockout mutant was sensitive to crude vegetable extracts, suggesting that the development of WzxE inhibitors could lead to novel food poisoning prevention agents. Considering previous findings that lipid-linked ECA repeat units are flipped by both WzxE and the flippase for colanic acid lipid-linked repeat-unit, the colanic acid-dependence of the\n                <jats:italic toggle=\"yes\">wzxE<\/jats:italic>\n                -knockout phenotype proposes a model in which a large amount of colanic acid under stress conditions occupies the flippase for colanic acid lipid-linked repeat unit, leading to accumulation of lipid-linked ECA repeat units on the inner membrane.\n              <\/jats:p>\n            <\/jats:sec>\n          <\/jats:sec>","DOI":"10.1128\/aem.02595-24","type":"journal-article","created":{"date-parts":[[2025,4,10]],"date-time":"2025-04-10T12:51:04Z","timestamp":1744289464000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":2,"title":["Enterobacterial common antigen repeat-unit flippase WzxE is required for\n            <i>Escherichia coli<\/i>\n            growth under acidic conditions, low temperature, and high osmotic stress conditions"],"prefix":"10.1128","volume":"91","author":[{"given":"Saki","family":"Yamaguchi","sequence":"first","affiliation":[{"name":"Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University","place":["Okayama, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0135-8891","authenticated-orcid":true,"given":"Kazuya","family":"Ishikawa","sequence":"additional","affiliation":[{"name":"Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University","place":["Okayama, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4068-8367","authenticated-orcid":true,"given":"Kazuyuki","family":"Furuta","sequence":"additional","affiliation":[{"name":"Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University","place":["Okayama, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2895-3386","authenticated-orcid":true,"given":"Chikara","family":"Kaito","sequence":"additional","affiliation":[{"name":"Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University","place":["Okayama, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.178.16.4885-4893.1996"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.75.103004.142545"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M611034200"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.183.12.3811-3815.2001"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2180-8-37"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.187.1.304-319.2005"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1042\/BSR20130018"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.178.4.1204-1206.1996"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/aem.60.2.740-745.1994"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01321-18"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M301750200"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.187.20.6917-6927.2005"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00461-06"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0005629"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF02996505"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)77373-0"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1021\/acschembio.0c00983"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.biochem.1c00314"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1111\/mmi.13284"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00550-16"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.11.1.142"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2002.02768.x"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/jcm.25.2.377-382.1987"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/msb4100050"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.120163297"},{"key":"e_1_3_2_27_2","volume-title":"Mycology guidebook","author":"Anonymous","year":"1974","unstructured":"Anonymous. 1974. Mycological Society of America. In Stevens RB (ed), Mycology guidebook. University of Washington Press."},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","unstructured":"Yamamoto R Ishikawa K Miyoshi Y Furuta K Miyoshi SI Kaito C. 2024. Overexpression of diglucosyldiacylglycerol synthase leads to daptomycin resistance in Bacillus subtilis. 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