{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T11:13:40Z","timestamp":1790766820670,"version":"4.1.0"},"reference-count":39,"publisher":"National Academy of Sciences","issue":"19","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2010,5,11]]},"abstract":"<jats:p>\n                    TcaR and IcaR are a weak and a strong negative regulator of transcription of the\n                    <jats:italic>ica<\/jats:italic>\n                    locus, respectively, and their presence prevents the poly-\n                    <jats:italic>N<\/jats:italic>\n                    -acetylglucosamine production and biofilm formation in\n                    <jats:italic>Staphylococcus epidermidis<\/jats:italic>\n                    . Although TcaR was shown to interact with the\n                    <jats:italic>ica<\/jats:italic>\n                    promoter, the precise binding region and the mechanism of interaction remained unclear. Here we present the 3D structure of TcaR in its apo form and in complex with salicylate as well as several aminoglycoside and \u03b2-lactam antibiotics. A comparison of the native and complex TcaR structures indicates that the mechanism of regulation involves a large conformational change in the DNA-binding lobe. Here, we deduced the consensus binding sequence of two [\u223cTTNNAA] hexamers embedded in a 16\u00a0bp sequence for a TcaR dimer. Six TcaR dimers bind specifically to three approximately 33\u00a0bp segments close to the IcaR binding region with varying affinities, and their repressor activity is directly interfered by salicylate and different classes of natural antimicrobial compounds. We also found in this study that the antimicrobial compounds we tested were shown not only to inhibit TcaR\u2013DNA interaction but also to further induce biofilm formation in\n                    <jats:italic>S. epidermidis<\/jats:italic>\n                    in our in vivo assay. The results support a general mechanism for antibiotics in regulating TcaR\u2013DNA interaction and thereby help understand the effect of antibiotic exposure on bacterial antibiotic resistance through biofilm formation.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0913302107","type":"journal-article","created":{"date-parts":[[2010,4,26]],"date-time":"2010-04-26T21:49:06Z","timestamp":1272318546000},"page":"8617-8622","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":89,"title":["Structural study of TcaR and its complexes with multiple antibiotics from\n                    <i>Staphylococcus epidermidis<\/i>"],"prefix":"10.1073","volume":"107","author":[{"given":"Yu-Ming","family":"Chang","sequence":"first","affiliation":[{"name":"Institute of Biochemical Sciences, National Taiwan University, Taipei 106, Taiwan; and"},{"name":"Institute of Biological Chemistry and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Yih","family":"Jeng","sequence":"additional","affiliation":[{"name":"Institute of Biological Chemistry and"},{"name":"Core Facility for Protein Crystallography, Academia Sinica, Taipei 115, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tzu-Ping","family":"Ko","sequence":"additional","affiliation":[{"name":"Institute of Biological Chemistry and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao-Jen","family":"Yeh","sequence":"additional","affiliation":[{"name":"Institute of Biochemical Sciences, National Taiwan University, Taipei 106, Taiwan; and"},{"name":"Institute of Biological Chemistry and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cammy K.-M.","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Biochemical Sciences, National Taiwan University, Taipei 106, Taiwan; and"},{"name":"Institute of Biological Chemistry and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew H.-J.","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Biochemical Sciences, National Taiwan University, Taipei 106, Taiwan; and"},{"name":"Institute of Biological Chemistry and"},{"name":"Core Facility for Protein Crystallography, Academia Sinica, Taipei 115, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2010,4,26]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"crossref","first-page":"1803","DOI":"10.1001\/jama.298.15.1803","article-title":"Antimicrobial resistance: It\u2019s not just for hospitals","volume":"298","author":"Bancroft EA","year":"2007","unstructured":"EA Bancroft, Antimicrobial resistance: It\u2019s not just for hospitals. 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Lancet 358, 135\u2013138 (2001).","journal-title":"Lancet"},{"key":"e_1_3_4_4_2","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.tim.2004.11.010","article-title":"Survival strategies of infectious biofilms","volume":"13","author":"Fux CA","year":"2005","unstructured":"CA Fux, JW Costerton, PS Stewart, P Stoodley, Survival strategies of infectious biofilms. Trends Microbiol 13, 34\u201340 (2005).","journal-title":"Trends Microbiol"},{"key":"e_1_3_4_5_2","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1046\/j.1462-5822.2004.00367.x","article-title":"Polysaccharide intercellular adhesin (PIA) protects Staphylococcus epidermidis against major components of the human innate immune system","volume":"6","author":"Vuong C","year":"2004","unstructured":"C Vuong, et al., Polysaccharide intercellular adhesin (PIA) protects Staphylococcus epidermidis against major components of the human innate immune system. Cell Microbiol 6, 269\u2013275 (2004).","journal-title":"Cell Microbiol"},{"key":"e_1_3_4_6_2","doi-asserted-by":"crossref","first-page":"2879","DOI":"10.1128\/JB.185.9.2879-2886.2003","article-title":"Glucose-related dissociation between icaADBC transcription and biofilm expression by Staphylococcus epidermidis: Evidence for an additional factor required for polysaccharide intercellular adhesin synthesis","volume":"185","author":"Dobinsky S","year":"2003","unstructured":"S Dobinsky, et al., Glucose-related dissociation between icaADBC transcription and biofilm expression by Staphylococcus epidermidis: Evidence for an additional factor required for polysaccharide intercellular adhesin synthesis. 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