{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T03:14:16Z","timestamp":1792120456760,"version":"4.4.0"},"reference-count":64,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2014,9,1]],"date-time":"2014-09-01T00:00:00Z","timestamp":1409529600000},"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":[[2014,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Brilacidin (PMX30063) has shown potent bactericidal activity against drug-resistant and -susceptible strains of multiple Gram-negative and Gram-positive pathogens. In this study, we demonstrate that brilacidin causes membrane depolarization in the Gram-positive bacterium\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Staphylococcus aureus<\/jats:named-content>\n            , to an extent comparable to that caused by the lipopeptidic drug daptomycin. Transcriptional profiling of\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Staphylococcus aureus<\/jats:named-content>\n            by deep sequencing shows that the global response to brilacidin treatment is well correlated to those of treatment with daptomycin and the cationic antimicrobial peptide LL37 and mostly indicates abrogation of cell wall and membrane functions. Furthermore, the upregulation of various chaperones and proteases by brilacidin and daptomycin indicates that cytoplasmic protein misfolding stress may be a contributor to the mechanism of action of these drugs. These stress responses were orchestrated mainly by three two-component systems, GraSR, VraSR, and NsaSR, which have been implicated in virulence and drug resistance against other clinically available antibiotics.\n          <\/jats:p>","DOI":"10.1128\/aac.02955-14","type":"journal-article","created":{"date-parts":[[2014,6,17]],"date-time":"2014-06-17T04:05:22Z","timestamp":1402977922000},"page":"5136-5145","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":184,"title":["Comparative Mechanistic Studies of Brilacidin, Daptomycin, and the Antimicrobial Peptide LL16"],"prefix":"10.1128","volume":"58","author":[{"given":"Bruk","family":"Mensa","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Chemistry and the Cardiovascular Research Institute, University of California, San Francisco, San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriella L.","family":"Howell","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry and the Cardiovascular Research Institute, University of California, San Francisco, San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Scott","sequence":"additional","affiliation":[{"name":"PolyMedix Inc., Radnor, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William F.","family":"DeGrado","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry and the Cardiovascular Research Institute, University of California, San Francisco, San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2477"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid0702.010206"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-065X.2000.917301.x"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0282(2000)55:1<4::AID-BIP30>3.0.CO;2-M"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/415389a"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro1098"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/bip.20917"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0966-842X(00)01823-0"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6968.2002.tb11000.x"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.peptides.2003.08.023"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1098\/rspb.2005.3301"},{"key":"e_1_3_3_13_2","first-page":"11","article-title":"Antimicrobial peptide resistance mechanisms of human bacterial pathogens","volume":"8","author":"Nizet V","year":"2006","unstructured":"NizetV. 2006. 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