{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,17]],"date-time":"2026-05-17T05:44:49Z","timestamp":1778996689786,"version":"3.51.4"},"reference-count":44,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2009,2,1]],"date-time":"2009-02-01T00:00:00Z","timestamp":1233446400000},"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":[[2009,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>We developed a screening procedure to identify small-molecule compounds that altered infection by<jats:italic>Listeria monocytogenes<\/jats:italic>to gain insights into bacterial\/host cellular processes required for intracellular pathogenesis. A small-molecule library of 480 compounds with known biological functions was screened, and 21 compounds that altered the<jats:italic>L. monocytogenes<\/jats:italic>infection of murine bone marrow-derived macrophages (BMM) were identified. The identified compounds affected various cellular functions, such as actin polymerization, kinase\/phosphatase activity, calcium signaling, and apoptosis. Pimozide, an FDA-approved drug used to treat severe Tourette's syndrome and schizophrenia, was further examined and shown to decrease the bacterial uptake and vacuole escape of<jats:italic>L. monocytogenes<\/jats:italic>in BMM. The inhibitory effect of pimozide on internalization was not specific for<jats:italic>L. monocytogenes<\/jats:italic>, as the phagocytosis of other bacterial species (<jats:italic>Bacillus subtilis<\/jats:italic>,<jats:italic>Salmonella enterica<\/jats:italic>serovar Typhimurium, and<jats:italic>Escherichia coli<\/jats:italic>K12) was significantly inhibited in the presence of pimozide. The invasion and cell-to-cell spread of<jats:italic>L. monocytogenes<\/jats:italic>during the infection of nonprofessional phagocytic cells also was decreased by pimozide treatment. Although pimozide has been reported to be an antagonist of mammalian cell calcium channels, the infection of BMM in a calcium-free medium did not relieve the inhibitory effects of pimozide on<jats:italic>L. monocytogenes<\/jats:italic>infection. Our results provide a generalizable screening approach for identifying small-molecule compounds that affect cellular pathways that are required for intracellular bacterial pathogenesis. We also have identified pimozide, a clinically approved antipsychotic drug, as a compound that may be suitable for further development as a therapeutic for intracellular bacterial infections.<\/jats:p>","DOI":"10.1128\/aac.00607-08","type":"journal-article","created":{"date-parts":[[2008,11,18]],"date-time":"2008-11-18T02:26:03Z","timestamp":1226975163000},"page":"756-764","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":43,"title":["A Small-Molecule Screen Identifies the Antipsychotic Drug Pimozide as an Inhibitor of<i>Listeria monocytogenes<\/i>Infection"],"prefix":"10.1128","volume":"53","author":[{"given":"Linda A.","family":"Lieberman","sequence":"first","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts 02115"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Darren E.","family":"Higgins","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts 02115"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1116008"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2006.00780.x"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2006.11.004"},{"key":"e_1_3_2_5_2","doi-asserted-by":"crossref","first-page":"4453","DOI":"10.4049\/jimmunol.163.8.4453","volume":"163","year":"1999","unstructured":"Caamano, J., J. 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