{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T01:57:02Z","timestamp":1791424622186,"version":"4.3.3"},"reference-count":70,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2014,10,28]],"date-time":"2014-10-28T00:00:00Z","timestamp":1414454400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-sa\/3.0\/"},{"start":{"date-parts":[[2014,12,31]],"date-time":"2014-12-31T00:00:00Z","timestamp":1419984000000},"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":["mBio"],"published-print":{"date-parts":[[2014,12,31]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Chaperone-usher pathway (CUP) pili are extracellular organelles produced by Gram-negative bacteria that mediate bacterial pathogenesis. Small-molecule inhibitors of CUP pili, termed pilicides, were rationally designed and shown to inhibit type 1 or P piliation. Here, we show that pilicide ec240 decreased the levels of type 1, P, and S piliation. Transcriptomic and proteomic analyses using the cystitis isolate UTI89 revealed that ec240 dysregulated CUP pili and decreased motility. Paradoxically, the transcript levels of P and S pilus genes were increased during growth in ec240, even though the level of P and S piliation decreased. In contrast, the most downregulated transcripts after growth in ec240 were from the type 1 pilus genes. Type 1 pilus expression is controlled by inversion of the\n                    <jats:italic>fimS<\/jats:italic>\n                    promoter element, which can oscillate between phase on and phase off orientations. ec240 induced the\n                    <jats:italic>fimS<\/jats:italic>\n                    phase off orientation, and this effect was necessary for the majority of ec240\u2019s inhibition of type 1 piliation. ec240 increased levels of the transcriptional regulators SfaB and PapB, which were shown to induce the\n                    <jats:italic>fimS<\/jats:italic>\n                    promoter phase off orientation. Furthermore, the effect of ec240 on motility was abolished in the absence of the SfaB, PapB, SfaX, and PapX regulators. In contrast to the effects of ec240, deletion of the type 1 pilus operon led to increased S and P piliation and motility. Thus, ec240 dysregulated several uropathogenic\n                    <jats:named-content content-type=\"genus-species\">Escherichia coli<\/jats:named-content>\n                    (UPEC) virulence factors through different mechanisms and independent of its effects on type 1 pilus biogenesis and may have potential as an antivirulence compound.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>IMPORTANCE<\/jats:bold>\n                    CUP pili and flagella play active roles in the pathogenesis of a variety of Gram-negative bacterial infections, including urinary tract infections mediated by UPEC. These are extremely common infections that are often recurrent and increasingly caused by antibiotic-resistant organisms. Preventing piliation and motility through altered regulation and assembly of these important virulence factors could aid in the development of novel therapeutics. This study increases our understanding of the regulation of these virulence factors, providing new avenues by which to target their expression.\n                  <\/jats:p>","DOI":"10.1128\/mbio.02038-14","type":"journal-article","created":{"date-parts":[[2014,10,28]],"date-time":"2014-10-28T21:49:03Z","timestamp":1414532943000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":76,"title":["Pilicide ec240 Disrupts Virulence Circuits in Uropathogenic Escherichia coli"],"prefix":"10.1128","volume":"5","author":[{"given":"Sarah E.","family":"Greene","sequence":"first","affiliation":[{"name":"Department of Molecular Microbiology and Microbial Pathogenesis and Center for Women\u2019s Infectious Disease Research, Washington University School of Medicine in St. Louis, St. Louis,\u00a0Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerome S.","family":"Pinkner","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Microbial Pathogenesis and Center for Women\u2019s Infectious Disease Research, Washington University School of Medicine in St. Louis, St. Louis,\u00a0Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik","family":"Chorell","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Microbial Pathogenesis and Center for Women\u2019s Infectious Disease Research, Washington University School of Medicine in St. Louis, St. Louis,\u00a0Missouri, USA"},{"name":"Department of Chemistry, Ume\u00e5 University, Ume\u00e5, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen W.","family":"Dodson","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Microbial Pathogenesis and Center for Women\u2019s Infectious Disease Research, Washington University School of Medicine in St. Louis, St. Louis,\u00a0Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carrie L.","family":"Shaffer","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville,\u00a0Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matt S.","family":"Conover","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Microbial Pathogenesis and Center for Women\u2019s Infectious Disease Research, Washington University School of Medicine in St. Louis, St. Louis,\u00a0Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Livny","sequence":"additional","affiliation":[{"name":"The Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge,\u00a0Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Hadjifrangiskou","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville,\u00a0Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fredrik","family":"Almqvist","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Ume\u00e5 University, Ume\u00e5, Sweden"},{"name":"Ume\u00e5 Center for Microbial Research, Ume\u00e5 University, Ume\u00e5, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott J.","family":"Hultgren","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Microbial Pathogenesis and Center for Women\u2019s Infectious Disease Research, Washington University School of Medicine in St. Louis, St. Louis,\u00a0Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1086\/524891"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1086\/591855"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3003021"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2004.02.010"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/342248a0"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.285.5430.1058"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.185.9.2723-2730.2003"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0052835"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.18.9827"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.54.3.761-767.1986"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.40.1.265-272.1983"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/19.12.2803"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.282.5393.1494"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2004.07.005"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2007.00952.x"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0900527106"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.0040329"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.160.2.691-695.1984"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.17.3.581-611.2004"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.82.17.5724"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.1996.311388.x"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2007.06025.x"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.84.18.6506"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1099\/jmm.0.05491-0"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.1994.tb00340.x"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000303"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2009.06919.x"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2001.02656.x"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/19.7.1450"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.micpath.2009.01.007"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00434-07"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.73.11.7588-7596.2005"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00630-08"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1002\/1439-7633(20011203)2:12<915::AID-CBIC915>3.3.CO;2-D"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio0109-1"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0606795103"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm100470t"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1021\/jo0704053"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2012.01.048"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1039\/c3ob42478b"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1039\/b509376g"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1039\/b613441f"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0600938103"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.159.2.762-766.1984"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)99895-9"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0902179106"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.18.8397"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00283-12"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0607898104"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.73.11.7657-7668.2005"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1937-6448(08)01402-0"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI113395"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.175.14.4335-4344.1993"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.169.8.3840-3843.1987"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M611502200"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.276.5312.607"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.ju.0000116123.05160.43"},{"key":"e_1_3_3_59_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.120163297"},{"key":"e_1_3_3_60_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.158.5.1713"},{"key":"e_1_3_3_61_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.172.9.5103-5111.1990"},{"key":"e_1_3_3_62_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/29.9.e45"},{"key":"e_1_3_3_63_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkn766"},{"key":"e_1_3_3_64_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp324"},{"key":"e_1_3_3_65_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2011.07.007"},{"key":"e_1_3_3_66_2","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2010-11-10-r106"},{"key":"e_1_3_3_67_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.54.3.613-620.1986"},{"key":"e_1_3_3_68_2","doi-asserted-by":"publisher","DOI":"10.1021\/ac026117i"},{"key":"e_1_3_3_69_2","doi-asserted-by":"publisher","DOI":"10.3102\/10769986027001077"},{"key":"e_1_3_3_70_2","doi-asserted-by":"publisher","DOI":"10.1016\/0378-1119(88)90440-4"},{"key":"e_1_3_3_71_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.1998.00797.x"}],"container-title":["mBio"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/mBio.02038-14","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/mBio.02038-14","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,7]],"date-time":"2022-03-07T20:49:07Z","timestamp":1646686147000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/mBio.02038-14"}},"subtitle":[],"editor":[{"given":"Ronald K.","family":"Taylor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2014,12,31]]},"references-count":70,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2014,12,31]]}},"alternative-id":["10.1128\/mBio.02038-14"],"URL":"https:\/\/doi.org\/10.1128\/mbio.02038-14","relation":{},"ISSN":["2161-2129","2150-7511"],"issn-type":[{"value":"2161-2129","type":"print"},{"value":"2150-7511","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,12,31]]},"assertion":[{"value":"2014-09-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-10-02","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-10-28","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e02038-14"}}