{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T11:38:43Z","timestamp":1790854723496,"version":"4.1.0"},"reference-count":66,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,1,17]],"date-time":"2025-01-17T00:00:00Z","timestamp":1737072000000},"content-version":"am","delay-in-days":16,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,1,17]],"date-time":"2025-01-17T00:00:00Z","timestamp":1737072000000},"content-version":"vor","delay-in-days":16,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100013759","name":"Commonwealth Health Research Board","doi-asserted-by":"publisher","award":["208\u201007\u201023"],"award-info":[{"award-number":["208\u201007\u201023"]}],"id":[{"id":"10.13039\/100013759","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["MCB\u20101919455"],"award-info":[{"award-number":["MCB\u20101919455"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["enviromicro-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Microbial Biotechnology"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The increasing threat of antibiotic resistance underscores the urgent need for innovative strategies to combat infectious diseases, including the development of antivirulants. Microbial pathogens rely on their virulence factors to initiate and sustain infections. Antivirulants are small molecules designed to target virulence factors, thereby attenuating the virulence of infectious microbes. The bacterial type IV pilus (T4P), an extracellular protein filament that depends on the T4P machinery (T4PM) for its biogenesis, dynamics and function, is a key virulence factor in many significant bacterial pathogens. While the T4PM presents a promising antivirulence target, the systematic identification of inhibitors for its multiple protein constituents remains a considerable challenge. Here we report a novel high\u2010throughput screening (HTS) approach for discovering T4P inhibitors. It uses\n                    <jats:italic>Pseudomonas aeruginosa,<\/jats:italic>\n                    a high\u2010priority pathogen, in combination with its T4P\u2010targeting phage, \u03c6KMV. Screening of a library of 2168 compounds using an optimised protocol led to the identification of tuspetinib, based on its deterrence of the lysis of\n                    <jats:italic>P.\u2009aeruginosa<\/jats:italic>\n                    by \u03c6KMV. Our findings show that tuspetinib also inhibits two additional T4P\u2010targeting phages, while having no effect on a phage that recognises lipopolysaccharides as its receptor. Additionally, tuspetinib impedes T4P\u2010mediated motility in\n                    <jats:italic>P.\u2009aeruginosa<\/jats:italic>\n                    and\n                    <jats:italic>Acinetobacter<\/jats:italic>\n                    species without impacting growth or flagellar motility. This bacterium\u2010phage pairing approach is applicable to a broad range of virulence factors that are required for phage infection, paving ways for the development of advanced chemotherapeutics against antibiotic\u2010resistant infections.\n                  <\/jats:p>","DOI":"10.1111\/1751-7915.70081","type":"journal-article","created":{"date-parts":[[2025,1,17]],"date-time":"2025-01-17T04:56:08Z","timestamp":1737089768000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["A Phage\u2010Based Approach to Identify Antivirulence Inhibitors of Bacterial Type\n                    <scp>IV<\/scp>\n                    Pili"],"prefix":"10.1111","volume":"18","author":[{"given":"Tori M.","family":"Shimozono","sequence":"first","affiliation":[{"name":"Department of Biological Sciences Virginia Tech  Blacksburg Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy J.","family":"Vogelaar","sequence":"additional","affiliation":[{"name":"Virginia Tech Center for Drug Discovery Virginia Tech  Blacksburg Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan T.","family":"O'Hara","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences Virginia Tech  Blacksburg Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2044-6793","authenticated-orcid":false,"given":"Zhaomin","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences Virginia Tech  Blacksburg Virginia USA"},{"name":"Virginia Tech Center for Drug Discovery Virginia Tech  Blacksburg Virginia USA"},{"name":"Center for Emerging, Zoonotic, and Arthropod\u2010Borne Pathogens Virginia Tech  Blacksburg Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,1,17]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1008393"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00834-08"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)02724-0"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1817757116"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.01390-09"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.186.10.3270-3273.2004"},{"key":"e_1_2_9_8_1","first-page":"150","volume-title":"Isolation and Characterization of Lytic Bacteriophages Infecting Pseudomonas aeruginosa","author":"Ceyssens P. 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