{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T01:07:49Z","timestamp":1783127269847,"version":"3.54.6"},"reference-count":45,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2013,1,1]],"date-time":"2013-01-01T00:00:00Z","timestamp":1356998400000},"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":[[2013,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Adenylate kinase (AK) is a ubiquitous intracellular enzyme that is released into the extracellular space upon cell lysis. We have shown that AK release serves as a useful reporter of bactericidal agent activity and can be exploited for antimicrobial screening purposes. The AK assay exhibits improved sensitivity over that of growth-based assays and can detect agents that are active against bacteria in clinically relevant growth states that are difficult to screen using conventional approaches, such as small colony variants (SCV) and bacteria within established biofilms. The usefulness of the AK assay was validated by screening a library of off-patent drugs for agents that exhibit antimicrobial properties toward a variety of bacterial species, including\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Escherichia coli<\/jats:named-content>\n            and all members of the \u201cESKAPE\u201d pathogens (E\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">nterococcus faecium<\/jats:named-content>\n            , S\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">taphylococcus aureus<\/jats:named-content>\n            , K\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">lebsiella pneumoniae<\/jats:named-content>\n            , A\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">cinetobacter baumannii<\/jats:named-content>\n            , P\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">seudomonas aeruginosa<\/jats:named-content>\n            , and E\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">nterobacter<\/jats:named-content>\n            species). The assay detected antibiotics within the library that were expected to be active against the organism screened. Moreover, 38 drugs with no previously reported antibacterial activity elicited AK release. Four of these were acquired, and all were verified to exhibit antimicrobial activity by standard susceptibility testing. Two of these molecules were further characterized. The antihistamine, terfenadine, was active against\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">S. aureus<\/jats:named-content>\n            planktonic, SCV population, and biofilm-associated cells. Tamoxifen, an estrogen receptor antagonist, was active toward\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">E. faecium<\/jats:named-content>\n            <jats:italic>in vitro<\/jats:italic>\n            and also reduced\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">E. faecium<\/jats:named-content>\n            pathogenesis in a\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Galleria mellonella<\/jats:named-content>\n            infection model. Our data demonstrate that the AK assay provides an attractive screening approach for identifying new antimicrobial agents. Further, terfenadine and tamoxifen may represent novel antimicrobial drug development scaffolds.\n          <\/jats:p>","DOI":"10.1128\/aac.01640-12","type":"journal-article","created":{"date-parts":[[2012,10,2]],"date-time":"2012-10-02T06:20:19Z","timestamp":1349158819000},"page":"26-36","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":61,"title":["Adenylate Kinase Release as a High-Throughput-Screening-Compatible Reporter of Bacterial Lysis for Identification of Antibacterial Agents"],"prefix":"10.1128","volume":"57","author":[{"given":"Anna C.","family":"Jacobs","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louis","family":"DiDone","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennielle","family":"Jobson","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madeline K.","family":"Sofia","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Damian","family":"Krysan","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, New York, USA"},{"name":"Department of Pediatrics, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul M.","family":"Dunman","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1086\/595011"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1086\/533452"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1086\/499819"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00030-10"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2201"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa042859"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.63.9.3373-3380.1995"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.170.9.4365-4372.1988"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10096-011-1396-6"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00889-09"},{"key":"e_1_3_3_12_2","first-page":"572","article-title":"Genetic recombination in Pseudomonas aeruginosa","volume":"13","author":"Holloway BW","year":"1955","unstructured":"HollowayBW. 1955. 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