{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T17:37:53Z","timestamp":1767980273081,"version":"3.49.0"},"reference-count":39,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2016,3,1]],"date-time":"2016-03-01T00:00:00Z","timestamp":1456790400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI065357"],"award-info":[{"award-number":["AI065357"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2016,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Burkholderia pseudomallei<\/jats:named-content>\n            is the etiologic agent of melioidosis, a difficult-to-treat disease with diverse clinical manifestations. \u03b2-Lactam antibiotics such as ceftazidime are crucial to the success of melioidosis therapy. Ceftazidime-resistant clinical isolates have been described, and the most common mechanism is point mutations affecting expression or critical amino acid residues of the chromosomally encoded class A PenA \u03b2-lactamase. We previously showed that PenA was exported via the twin arginine translocase system and associated with the spheroplast fraction. We now show that PenA is a membrane-bound lipoprotein. The protein and accompanying \u03b2-lactamase activity are found in the membrane fraction and can be extracted with Triton X-114. Treatment with globomycin of\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">B. pseudomallei<\/jats:named-content>\n            cells expressing PenA results in accumulation of the prolipoprotein. Mass spectrometric analysis of extracted membrane proteins reveals a protein peak whose mass is consistent with a triacylated PenA protein. Mutation of a crucial lipobox cysteine at position 23 to a serine residue results in loss of \u03b2-lactamase activity and absence of detectable PenA\n            <jats:sub>C23S<\/jats:sub>\n            protein. A concomitant isoleucine-to-alanine change at position 20 in the signal peptide processing site in the PenA\n            <jats:sub>C23S<\/jats:sub>\n            mutant results in a nonlipidated protein (PenA\n            <jats:sub>I20A C23S<\/jats:sub>\n            ) that is processed by signal peptidase I and exhibits \u03b2-lactamase activity. The resistance profile of a\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">B. pseudomallei<\/jats:named-content>\n            strain expressing this protein is indistinguishable from the profile of the isogenic strain expressing wild-type PenA. The data show that PenA membrane association is not required for resistance and must serve another purpose.\n          <\/jats:p>","DOI":"10.1128\/aac.02444-15","type":"journal-article","created":{"date-parts":[[2015,12,29]],"date-time":"2015-12-29T03:23:15Z","timestamp":1451359395000},"page":"1509-1514","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":25,"title":["Membrane-Bound PenA \u03b2-Lactamase of Burkholderia pseudomallei"],"prefix":"10.1128","volume":"60","author":[{"given":"Linnell B.","family":"Randall","sequence":"first","affiliation":[{"name":"Department of Molecular Genetics and Microbiology, Emerging Pathogens Institute, University of Florida, Gainesville, Florida, USA"},{"name":"Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, Colorado, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karen","family":"Dobos","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, Colorado, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Krisztina M.","family":"Papp-Wallace","sequence":"additional","affiliation":[{"name":"Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, Ohio, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert A.","family":"Bonomo","sequence":"additional","affiliation":[{"name":"Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, Ohio, USA"},{"name":"Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA"},{"name":"Department of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA"},{"name":"Department of Molecular Biology and Microbiology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Herbert P.","family":"Schweizer","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics and Microbiology, Emerging Pathogens Institute, University of Florida, Gainesville, Florida, USA"},{"name":"Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, Colorado, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1204699"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1586\/14787210.4.3.445"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.2217\/fmb.12.116"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2014.01.005"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(89)90768-X"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid1812.120638"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.05517-11"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.47.7.2082-2087.2003"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.01657-08"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2011.00139"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0030789"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.2147\/IDR.S35529"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1111020108"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.458315"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/20.3.313"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01313-09"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.01669-09"},{"key":"e_1_3_3_19_2","volume-title":"Performance standards for antimicrobial susceptibility testing: twenty-fifth informal supplement M100-S25","author":"Clinical and Laboratory Standards Institute","year":"2015","unstructured":"Clinical and Laboratory Standards Institute. 2015. 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Clinical and Laboratory Standards Institute, Wayne, PA."},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.02430-07"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00682-10"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)88911-6"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)85762-9"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.160.3.1181-1183.1984"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.56.2.490-498.1988"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)69848-0"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.59.9.3163-3168.1991"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.60.4.1336-1342.1992"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.67.9.4960-4962.1999"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.70.8.4106-4111.2002"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1110\/ps.0303703"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2007.06.020"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.181.16.5090-5093.1999"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1002\/pro.697"},{"key":"e_1_3_3_35_2","volume-title":"Abstr 54th Intersci Conf Antimicrob Agents Chemother","author":"Gonzalez L","year":"2014","unstructured":"Gonzalez L, Bahr G, Bonomo RA, Vila A. 2014. Membrane anchoring of carbapenemase Ndm-1 favors protein stability and resistance transfer, abstr C162c. Abstr 54th Intersci Conf Antimicrob Agents Chemother. 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