{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T12:12:17Z","timestamp":1764331937967},"reference-count":61,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2011,9,1]],"date-time":"2011-09-01T00:00:00Z","timestamp":1314835200000},"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":[[2011,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Numerous bacterial pathogens, particularly those that colonize fast-flow areas in the bladder and gastrointestinal tract, require motility to establish infection and spread beyond the initially colonized tissue.<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Vibrio cholerae<\/jats:named-content>strains of serogroups O1 and O139, the causative agents of the diarrheal illness cholera, express a single polar flagellum powered by sodium motive force and require motility to colonize and spread along the small intestine. Therefore, motility may be an attractive target for small molecules that can prevent and\/or block the infective process. In this study, we describe a high-throughput screening (HTS) assay to identify small molecules that selectively inhibit bacterial motility. The HTS assay was used to screen an \u223c8,000-compound structurally diverse chemical library for inhibitors of<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">V. cholerae<\/jats:named-content>motility. The screen identified a group of quinazoline-2,4-diamino analogs that completely suppressed motility without affecting the growth rate in broth. A further study on the effects of one analog, designated Q24DA, showed that it induces a flagellated but nonmotile (Mot<jats:sup>\u2212<\/jats:sup>) phenotype and is specific for the Na<jats:sup>+<\/jats:sup>-driven flagellar motor of pathogenic<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Vibrio<\/jats:named-content>species. A mutation conferring phenamil-resistant motility did not eliminate inhibition of motility by Q24DA. Q24DA diminished the expression of cholera toxin and toxin-coregulated pilus as well as biofilm formation and fluid secretion in the rabbit ileal loop model. Furthermore, treatment of<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">V. cholerae<\/jats:named-content>with Q24DA impacted additional phenotypes linked to Na<jats:sup>+<\/jats:sup>bioenergetics, such as the function of the primary Na<jats:sup>+<\/jats:sup>pump, Nqr, and susceptibility to fluoroquinolones. The above results clearly show that the described HTS assay is capable of identifying small molecules that specifically block bacterial motility. New inhibitors such as Q24DA may be instrumental in probing the molecular architecture of the Na<jats:sup>+<\/jats:sup>-driven polar flagellar motor and in studying the role of motility in the expression of other virulence factors.<\/jats:p>","DOI":"10.1128\/aac.00482-11","type":"journal-article","created":{"date-parts":[[2011,6,28]],"date-time":"2011-06-28T09:04:00Z","timestamp":1309251840000},"page":"4134-4143","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":44,"title":["A High-Throughput Screening Assay for Inhibitors of Bacterial Motility Identifies a Novel Inhibitor of the Na<sup>+<\/sup>-Driven Flagellar Motor and Virulence Gene Expression in Vibrio cholerae"],"prefix":"10.1128","volume":"55","author":[{"given":"Lynn","family":"Rasmussen","sequence":"first","affiliation":[{"name":"Southern Research Institute, 2000 Ninth Avenue South, Birmingham, Alabama 35205"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E. Lucile","family":"White","sequence":"additional","affiliation":[{"name":"Southern Research Institute, 2000 Ninth Avenue South, Birmingham, Alabama 35205"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ashish","family":"Pathak","sequence":"additional","affiliation":[{"name":"Southern Research Institute, 2000 Ninth Avenue South, Birmingham, Alabama 35205"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julio C.","family":"Ayala","sequence":"additional","affiliation":[{"name":"Southern Research Institute, 2000 Ninth Avenue South, Birmingham, Alabama 35205"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongxia","family":"Wang","sequence":"additional","affiliation":[{"name":"Southern Research Institute, 2000 Ninth Avenue South, Birmingham, Alabama 35205"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jian-He","family":"Wu","sequence":"additional","affiliation":[{"name":"Morehouse School of Medicine, 720 Westview Dr., SW, Atlanta, Georgia 30310"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jorge A.","family":"Benitez","sequence":"additional","affiliation":[{"name":"Southern Research Institute, 2000 Ninth Avenue South, Birmingham, Alabama 35205"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anisia J.","family":"Silva","sequence":"additional","affiliation":[{"name":"Morehouse School of Medicine, 720 Westview Dr., SW, Atlanta, Georgia 30310"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.179.16.5104-5110.1997"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.172.3.1634-1639.1990"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.179.12.4043-4045.1997"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.72.121801.161737"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.femsle.2004.08.039"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.182.4.1035-1045.2000"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0308052101"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.186.14.4613-4619.2004"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.187.9.3158-3170.2005"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2000.01745.x"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.187.18.6324-6332.2005"},{"key":"e_1_3_3_13_2","first-page":"478","article-title":"Trend of antibiotic resistance of Vibrio cholerae strains from east Delhi","volume":"127","author":"Das S.","year":"2008","unstructured":"DasS. SahaR. KaurI. R.. 2008. Trend of antibiotic resistance of Vibrio cholerae strains from east Delhi. Indian J. Med. Res. 127:478\u2013482.","journal-title":"Indian J. Med. Res"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/path.1700660228"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4757-9688-9_8"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.64.6.2246-2255.1996"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.182.15.4234-4240.2000"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00843-08"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1099\/00221287-147-4-831"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0005-2728(00)00286-3"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.6.3183"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/MMBR.65.3.353-370.2001"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.168.4.1487"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1348-0421.2003.tb03379.x"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6968.2001.tb10847.x"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.187.24.8403-8410.2005"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1348-0421.1986.tb03037.x"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.10.5740"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.8.1.48"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.182.13.3693-3704.2000"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.180.2.303-316.1998"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.180.19.5256-5259.1998"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.1998.00809.x"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2007.05623.x"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.181.6.1927-1930.1999"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1998.2377"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.186.15.4864-4874.2004"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.111581598"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1177\/1087057107304478"},{"key":"e_1_3_3_40_2","first-page":"51","article-title":"The multiple identities of Vibrio parahaemolyticus","volume":"1","author":"McCarter L. L.","year":"1999","unstructured":"McCarterL. L. 1999. The multiple identities of Vibrio parahaemolyticus. J. Mol. Microbiol. Biotechnol. 1:51\u201357.","journal-title":"J. Mol. Microbiol. Biotechnol"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1128\/MMBR.65.3.445-462.2001"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1159\/000077866"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00948-09"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1017\/S0950268806007254"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.0020109"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid1311.070674"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.1997.4281787.x"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.19.2.382-402.2006"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2001.02348.x"},{"key":"e_1_3_3_50_2","doi-asserted-by":"crossref","first-page":"128","DOI":"10.7883\/yoken.JJID.2008.128","article-title":"Emergence of tetracycline-resistant Vibrio cholerae O1 serotype Inaba, in Kolkata, India","volume":"61","author":"Roychowdhury A.","year":"2008","unstructured":"RoychowdhuryA. . 2008. Emergence of tetracycline-resistant Vibrio cholerae O1 serotype Inaba, in Kolkata, India. Jpn. J. Infect. Dis. 61:128\u2013129.","journal-title":"Jpn. J. Infect. Dis"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0915164107"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.172.1.334-341.1990"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.74.4.2072-2079.2006"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00460-06"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi9009083"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)68465-0"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00949-09"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00948-08"},{"key":"e_1_3_3_59_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.1999.01624.x"},{"key":"e_1_3_3_60_2","doi-asserted-by":"publisher","DOI":"10.1128\/aem.59.2.541-546.1993"},{"key":"e_1_3_3_61_2","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M600228-MCP200"},{"key":"e_1_3_3_62_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.052694299"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.00482-11","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.00482-11","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,6,7]],"date-time":"2023-06-07T21:07:17Z","timestamp":1686172037000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.00482-11"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,9]]},"references-count":61,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2011,9]]}},"alternative-id":["10.1128\/AAC.00482-11"],"URL":"https:\/\/doi.org\/10.1128\/aac.00482-11","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,9]]},"assertion":[{"value":"2011-04-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2011-06-15","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2011-08-17","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}