{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T15:54:22Z","timestamp":1790610862315,"version":"4.1.0"},"reference-count":42,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2003,11,1]],"date-time":"2003-11-01T00:00:00Z","timestamp":1067644800000},"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":[[2003,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Staphylococci often form biofilms, sessile communities of microcolonies encased in an extracellular matrix that adhere to biomedical implants or damaged tissue. Infections associated with biofilms are difficult to treat, and it is estimated that sessile bacteria in biofilms are 1,000 to 1,500 times more resistant to antibiotics than their planktonic counterparts. This antibiotic resistance of biofilms often leads to the failure of conventional antibiotic therapy and necessitates the removal of infected devices. Lysostaphin is a glycylglycine endopeptidase which specifically cleaves the pentaglycine cross bridges found in the staphylococcal peptidoglycan. Lysostaphin kills\n            <jats:italic>Staphylococcus aureus<\/jats:italic>\n            within minutes (MIC at which 90% of the strains are inhibited [MIC\n            <jats:sub>90<\/jats:sub>\n            ], 0.001 to 0.064 \u03bcg\/ml) and is also effective against\n            <jats:italic>Staphylococcus epidermidis<\/jats:italic>\n            at higher concentrations (MIC\n            <jats:sub>90<\/jats:sub>\n            , 12.5 to 64 \u03bcg\/ml). The activity of lysostaphin against staphylococci present in biofilms compared to those of other antibiotics was, however, never explored. Surprisingly, lysostaphin not only killed\n            <jats:italic>S. aureus<\/jats:italic>\n            in biofilms but also disrupted the extracellular matrix of\n            <jats:italic>S. aureus<\/jats:italic>\n            biofilms in vitro on plastic and glass surfaces at concentrations as low as 1 \u03bcg\/ml. Scanning electron microscopy confirmed that lysostaphin eradicated both the sessile cells and the extracellular matrix of the biofilm. This disruption of\n            <jats:italic>S. aureus<\/jats:italic>\n            biofilms was specific for lysostaphin-sensitive\n            <jats:italic>S. aureus<\/jats:italic>\n            , as biofilms of lysostaphin-resistant\n            <jats:italic>S. aureus<\/jats:italic>\n            were not affected. High concentrations of oxacillin (400 \u03bcg\/ml), vancomycin (800 \u03bcg\/ml), and clindamycin (800 \u03bcg\/ml) had no effect on the established\n            <jats:italic>S. aureus<\/jats:italic>\n            biofilms in this system, even after 24 h. Higher concentrations of lysostaphin also disrupted\n            <jats:italic>S. epidermidis<\/jats:italic>\n            biofilms.\n          <\/jats:p>","DOI":"10.1128\/aac.47.11.3407-3414.2003","type":"journal-article","created":{"date-parts":[[2003,10,24]],"date-time":"2003-10-24T02:33:30Z","timestamp":1066962810000},"page":"3407-3414","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":249,"title":["Lysostaphin Disrupts\n            <i>Staphylococcus aureus<\/i>\n            and\n            <i>Staphylococcus epidermidis<\/i>\n            Biofilms on Artificial Surfaces"],"prefix":"10.1128","volume":"47","author":[{"given":"Julie A.","family":"Wu","sequence":"first","affiliation":[{"name":"Biosynexus Incorporated, Gaithersburg, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Kusuma","sequence":"additional","affiliation":[{"name":"Biosynexus Incorporated, Gaithersburg, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James J.","family":"Mond","sequence":"additional","affiliation":[{"name":"Biosynexus Incorporated, Gaithersburg, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John F.","family":"Kokai-Kun","sequence":"additional","affiliation":[{"name":"Biosynexus Incorporated, Gaithersburg, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/44.1.43"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0142-9612(00)00390-2"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(65)90473-0"},{"key":"e_1_3_2_5_2","unstructured":"Centers for Disease Control and Prevention. 1998. Preventing emerging infectious diseases: a strategy for the 21st century. Centers for Disease Control and Prevention Atlanta Ga."},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/hc3401.095097"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/jcm.22.6.996-1006.1985"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.45.5.1431-1437.2001"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.42.6.1355"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0924-8579(99)00018-7"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.284.5418.1318"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.183.9.2888-2896.2001"},{"key":"e_1_3_2_13_2","first-page":"1432","volume":"41","year":"2000","unstructured":"Dajcs, J., E. Hume, J. Moreau, A. Caballero, B. Cannon, and R. O'Callaghan. 2000. Lysostaphin treatment of methicillin-resistant Staphylococcus aureus keratitis in rabbits. Investig. Ophthalmol. Vis. Sci.41:1432-1437.","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.40.02.382-388.2002"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0142-9612(98)00096-9"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.15.2.167-193.2002"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.39.2.750-753.2001"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.15.2.155-166.2002"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/46.1.61"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.69.5.3423-3426.2001"},{"key":"e_1_3_2_21_2","first-page":"103","volume":"39","year":"1997","unstructured":"Hamilton-Miller, J., and S. Shah. 1997. Activity of quinupristin\/dalfopristin against Staphylococcus epidermidis in biofilms: a comparison with ciprofloxacin. J. Antimicrob. Chemother.39:103-108.","journal-title":"J. Antimicrob. 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Pascual, L. Martinez-Martinez, and E. Perea. 1994. Activity of eight antibacterial agents on Staphylococcus epidermidis attached to Teflon catheters. J. Med. Microbiol.10:43-47.","journal-title":"J. Med. Microbiol."},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/41.2.155"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0142-9612(96)00199-8"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.51.3.414"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1097\/00003226-200105000-00005"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.295.5559.1487"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1097\/00003086-199611000-00025"},{"key":"e_1_3_2_43_2","first-page":"309","volume":"16","year":"1972","unstructured":"Zygmunt, W., and P. Tavormina. 1972. Lysostaphin: model for specific enzymatic approach to infectious disease. Prog. 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