{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T21:32:26Z","timestamp":1791840746307,"version":"4.3.4"},"reference-count":53,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2012,10,1]],"date-time":"2012-10-01T00:00:00Z","timestamp":1349049600000},"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":[[2012,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Bacterial biofilm formation is responsible for numerous chronic infections, causing a severe health burden. Many of these infections cannot be resolved, as bacteria in biofilms are resistant to the host's immune defenses and antibiotic therapy. New strategies to treat biofilm-based infections are critically needed. Cyclic di-GMP (c-di-GMP) is a widely conserved second-messenger signal essential for biofilm formation. As this signaling system is found only in bacteria, it is an attractive target for the development of new antibiofilm interventions. Here, we describe the results of a high-throughput screen to identify small-molecule inhibitors of diguanylate cyclase (DGC) enzymes that synthesize c-di-GMP. We report seven small molecules that antagonize these enzymes and inhibit biofilm formation by\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Vibrio cholerae<\/jats:named-content>\n            . Moreover, two of these compounds significantly reduce the total concentration of c-di-GMP in\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">V. cholerae<\/jats:named-content>\n            , one of which also inhibits biofilm formation by\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Pseudomonas aeruginosa<\/jats:named-content>\n            in a continuous-flow system. These molecules represent the first compounds described that are able to inhibit DGC activity to prevent biofilm formation.\n          <\/jats:p>","DOI":"10.1128\/aac.01396-12","type":"journal-article","created":{"date-parts":[[2012,7,31]],"date-time":"2012-07-31T07:47:26Z","timestamp":1343720846000},"page":"5202-5211","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":134,"title":["Identification of Small Molecules That Antagonize Diguanylate Cyclase Enzymes To Inhibit Biofilm Formation"],"prefix":"10.1128","volume":"56","author":[{"given":"Karthik","family":"Sambanthamoorthy","sequence":"first","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rudolph E.","family":"Sloup","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vijay","family":"Parashar","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, UMDNJ-New Jersey Medical School, Newark, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua M.","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric E.","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Princeton University, Princeton, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin F.","family":"Semmelhack","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Princeton University, Princeton, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew B.","family":"Neiditch","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, UMDNJ-New Jersey Medical School, Newark, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher M.","family":"Waters","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00564-08"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/ppul.21011"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2010.07470.x"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0406134101"},{"key":"e_1_3_2_6_2","doi-asserted-by":"crossref","first-page":"2279","DOI":"10.2174\/138161210791792868","article-title":"Biofilms: an extra hurdle for effective antimicrobial therapy","volume":"16","author":"Cos P","year":"2010","unstructured":"CosP ToteK HoremansT MaesL. 2010. Biofilms: an extra hurdle for effective antimicrobial therapy. Curr. Pharm. Des. 16:2279\u20132295.","journal-title":"Curr. Pharm. Des."},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2006.12.006"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.0060067"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1094\/MPMI-19-1378"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-2920.2004.00633.x"},{"key":"e_1_3_2_11_2","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1021\/ja207742q","article-title":"Oligomer formation of the bacterial second messenger c-di-GMP: reaction rates and equilibrium constants indicate a monomeric state at physiological concentrations","volume":"134","author":"Gentner M","year":"2012","unstructured":"GentnerM AllanMG ZaehringerF SchirmerT GrzesiekS. 2012. Oligomer formation of the bacterial second messenger c-di-GMP: reaction rates and equilibrium constants indicate a monomeric state at physiological concentrations. J. Am. Chem. Soc. 134:1019\u20131029.","journal-title":"J. Am. Chem. Soc."},{"key":"e_1_3_2_12_2","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1021\/cc9800071","article-title":"A knowledge-based approach in designing combinatorial or medicinal chemistry libraries for drug discovery. 1. A qualitative and quantitative characterization of known drug databases","volume":"1","author":"Ghose AK","year":"1999","unstructured":"GhoseAK ViswanadhanVN WendoloskiJJ. 1999. A knowledge-based approach in designing combinatorial or medicinal chemistry libraries for drug discovery. 1. A qualitative and quantitative characterization of known drug databases. J. Comb Chem. 1:55\u201368.","journal-title":"J. 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Identification of a novel triterpenoid saponin from Pisum sativum as a specific inhibitor of the diguanylate cyclase of Acetobacter xylinum. Plant Cell Physiol. 39:144\u2013152.","journal-title":"Plant Cell Physiol."},{"key":"e_1_3_2_33_2","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1093\/oxfordjournals.pcp.a029352","article-title":"Glycosylated triterpenoid saponin: a specific inhibitor of diguanylate cyclase from Acetobacter xylinum. Biological activity and distribution","volume":"39","author":"Ohana P","year":"1998","unstructured":"OhanaP DelmerDP VolmanG BenzimanM. 1998. Glycosylated triterpenoid saponin: a specific inhibitor of diguanylate cyclase from Acetobacter xylinum. Biological activity and distribution. 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