{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:46:54Z","timestamp":1791334014660,"version":"4.3.1"},"reference-count":33,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2014,4,1]],"date-time":"2014-04-01T00:00:00Z","timestamp":1396310400000},"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":[[2014,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            The Gram-negative human pathogen\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Pseudomonas aeruginosa<\/jats:named-content>\n            tolerates high concentrations of \u03b2-lactam antibiotics. Despite inhibiting the growth of the organism, these cell wall-targeting drugs exhibit remarkably little bactericidal activity. However, the mechanisms underlying \u03b2-lactam tolerance are currently unclear. Here, we show that\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">P. aeruginosa<\/jats:named-content>\n            undergoes a rapid\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">en masse<\/jats:named-content>\n            transition from normal rod-shaped cells to viable cell wall-defective spherical cells when treated with \u03b2-lactams from the widely used carbapenem and penicillin classes. When the antibiotic is removed, the entire population of spherical cells quickly converts back to the normal bacillary form. Our results demonstrate that these rapid population-wide cell morphotype transitions function as a strategy to survive antibiotic exposure. Taking advantage of these findings, we have developed a novel approach to efficiently kill\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">P. aeruginosa<\/jats:named-content>\n            by using carbapenem treatment to induce\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">en masse<\/jats:named-content>\n            transition to the spherical cell morphotype and then exploiting the relative fragility and sensitivity of these cells to killing by antimicrobial peptides (AMPs) that are relatively inactive against\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">P. aeruginosa<\/jats:named-content>\n            bacillary cells. This approach could broaden the repertoire of antimicrobial compounds used to treat\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">P. aeruginosa<\/jats:named-content>\n            and serve as a basis for developing new therapeutic agents to combat bacterial infections.\n          <\/jats:p>","DOI":"10.1128\/aac.01901-13","type":"journal-article","created":{"date-parts":[[2014,1,14]],"date-time":"2014-01-14T05:33:01Z","timestamp":1389677581000},"page":"1956-1962","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":87,"title":["Rapid Conversion of Pseudomonas aeruginosa to a Spherical Cell Morphotype Facilitates Tolerance to Carbapenems and Penicillins but Increases Susceptibility to Antimicrobial Peptides"],"prefix":"10.1128","volume":"58","author":[{"given":"Leigh G.","family":"Monahan","sequence":"first","affiliation":[{"name":"The ithree institute, University of Technology Sydney, Ultimo, NSW, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynne","family":"Turnbull","sequence":"additional","affiliation":[{"name":"The ithree institute, University of Technology Sydney, Ultimo, NSW, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah R.","family":"Osvath","sequence":"additional","affiliation":[{"name":"The ithree institute, University of Technology Sydney, Ultimo, NSW, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debra","family":"Birch","sequence":"additional","affiliation":[{"name":"Microscopy Unit, Faculty of Science, Macquarie University, North Ryde, NSW, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian G.","family":"Charles","sequence":"additional","affiliation":[{"name":"The ithree institute, University of Technology Sydney, Ultimo, NSW, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia B.","family":"Whitchurch","sequence":"additional","affiliation":[{"name":"The ithree institute, University of Technology Sydney, Ultimo, NSW, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2011.00065"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd3267"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0463.2009.02563.x"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.20506\/rst.31.1.2096"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/clinids\/10.4.699"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/clinids\/8.Supplement_3.S260"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/s100960050180"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/41.4.435"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.9.6.1033"},{"key":"e_1_3_3_11_2","first-page":"74","article-title":"Effect of carbenicillin on Pseudomonas aeruginosa","volume":"101","author":"Chadwick P","year":"1969","unstructured":"ChadwickP. 1969. Effect of carbenicillin on Pseudomonas aeruginosa. Can. Med. Assoc. J. 101:74\u201380.","journal-title":"Can. Med. Assoc. J."},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.27.1.1"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.diagmicrobio.2005.02.010"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1086\/426189"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.49.12.4920-4927.2005"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.01138-07"},{"key":"e_1_3_3_17_2","volume-title":"Approved standard M7-A6","author":"Clinical and Laboratory Standards Institute","year":"2003","unstructured":"Clinical and Laboratory Standards Institute. 2003. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically, 6th ed. Approved standard M7-A6. 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