{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T21:31:38Z","timestamp":1793136698214,"version":"4.5.0"},"reference-count":79,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2018,8,7]],"date-time":"2018-08-07T00:00:00Z","timestamp":1533600000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2018,9,5]],"date-time":"2018-09-05T00:00:00Z","timestamp":1536105600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000057","name":"HHS | NIH | National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["GM118024"],"award-info":[{"award-number":["GM118024"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"HHS | NIH | National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["F32GM116188"],"award-info":[{"award-number":["F32GM116188"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2018,9,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Gram-negative bacteria have an outer membrane (OM) impermeable to many toxic compounds that can be further strengthened during stress. In\n            <jats:italic>Enterobacteriaceae<\/jats:italic>\n            , the envelope contains enterobacterial common antigen (ECA), a carbohydrate-derived moiety conserved throughout\n            <jats:italic>Enterobacteriaceae<\/jats:italic>\n            , the function of which is poorly understood. Previously, we identified several genes in\n            <jats:named-content content-type=\"genus-species\">Escherichia coli<\/jats:named-content>\n            K-12 responsible for an RpoS-dependent decrease in envelope permeability during carbon-limited stationary phase. For one of these,\n            <jats:italic>yhdP<\/jats:italic>\n            , a gene of unknown function, deletion causes high levels of both vancomycin and detergent sensitivity, independent of growth phase. We isolated spontaneous suppressor mutants of\n            <jats:italic>yhdP<\/jats:italic>\n            with loss-of-function mutations in the ECA biosynthesis operon. ECA biosynthesis gene deletions suppressed envelope permeability from\n            <jats:italic>yhdP<\/jats:italic>\n            deletion independently of envelope stress responses and interactions with other biosynthesis pathways, demonstrating suppression is caused directly by removing ECA. Furthermore,\n            <jats:italic>yhdP<\/jats:italic>\n            deletion changed cellular ECA levels and\n            <jats:italic>yhdP<\/jats:italic>\n            was found to co-occur phylogenetically with the ECA biosynthesis operon. Cells make three forms of ECA: ECA lipopolysaccharide (LPS), an ECA chain linked to LPS core; ECA phosphatidylglycerol, a surface-exposed ECA chain linked to phosphatidylglycerol; and cyclic ECA, a cyclized soluble ECA molecule found in the periplasm. We determined that the suppression of envelope permeability with\n            <jats:italic>yhdP<\/jats:italic>\n            deletion is caused specifically by the loss of cyclic ECA, despite lowered levels of this molecule found with\n            <jats:italic>yhdP<\/jats:italic>\n            deletion. Furthermore, removing cyclic ECA from wild-type cells also caused changes to OM permeability. Our data demonstrate cyclic ECA acts to maintain the OM permeability barrier in a manner controlled by YhdP.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            Enterobacterial common antigen (ECA) is a surface antigen made by all members of\n            <jats:italic>Enterobacteriaceae<\/jats:italic>\n            , including many clinically relevant genera (e.g.,\n            <jats:italic>Escherichia<\/jats:italic>\n            ,\n            <jats:italic>Klebsiella<\/jats:italic>\n            ,\n            <jats:italic>Yersinia<\/jats:italic>\n            ). Although this surface-exposed molecule is conserved throughout\n            <jats:italic>Enterobacteriaceae<\/jats:italic>\n            , very few functions have been ascribed to it. Here, we have determined that the periplasmic form of ECA, cyclic ECA, plays a role in maintaining the outer membrane permeability barrier. This activity is controlled by a protein of unknown function, YhdP, and deletion of\n            <jats:italic>yhdP<\/jats:italic>\n            damages the OM permeability barrier in a cyclic ECA-dependent manner, allowing harmful molecules such as antibiotics into the cell. This role in maintenance of the envelope permeability barrier is the first time a phenotype has been described for cyclic ECA. As the Gram-negative envelope is generally impermeable to antibiotics, understanding the mechanisms through which the barrier is maintained and antibiotics are excluded may lead to improved antibiotic delivery.\n          <\/jats:p>","DOI":"10.1128\/mbio.01321-18","type":"journal-article","created":{"date-parts":[[2018,8,6]],"date-time":"2018-08-06T09:54:49Z","timestamp":1533549289000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":81,"title":["Cyclic Enterobacterial Common Antigen Maintains the Outer Membrane Permeability Barrier of Escherichia coli in a Manner Controlled by YhdP"],"prefix":"10.1128","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1062-0716","authenticated-orcid":false,"given":"Angela M.","family":"Mitchell","sequence":"first","affiliation":[{"name":"Department of Molecular Biology, Princeton University, Princeton, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tharan","family":"Srikumar","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Princeton University, Princeton, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas J.","family":"Silhavy","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Princeton University, Princeton, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a000414"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.71.110601.135414"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/MMBR.67.4.593-656.2003"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6968.1988.tb02743.x"},{"key":"e_1_3_2_6_2","volume-title":"Antimicrobial resistance: global report on surveillance","author":"World Health Organization","year":"2014","unstructured":"World Health Organization. 2014. 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