{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T00:26:22Z","timestamp":1793406382446,"version":"4.5.0"},"reference-count":43,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,8,19]],"date-time":"2021-08-19T00:00:00Z","timestamp":1629331200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,8,19]],"date-time":"2021-08-19T00:00:00Z","timestamp":1629331200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"the National Key R&D Program of China","award":["2017YFC1309301"],"award-info":[{"award-number":["2017YFC1309301"]}]},{"name":"the National Key R&D Program of China","award":["2017YFC1309300"],"award-info":[{"award-number":["2017YFC1309300"]}]},{"name":"the CAMS Innovation Fund for Medical Sciences","award":["CIFMS 2018-I2M-1\u2013003"],"award-info":[{"award-number":["CIFMS 2018-I2M-1\u2013003"]}]},{"name":"the National Science Grant for Distinguished Young Scholars","award":["81425001\/H0104"],"award-info":[{"award-number":["81425001\/H0104"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Microbiol"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Resistance to ceftazidime-avibactam was reported<jats:bold>,<\/jats:bold> and it is important to investigate the mechanisms of ceftazidime\/avibactam resistance in <jats:italic>K. pneumoniae<\/jats:italic> with mutations in <jats:italic>bla<\/jats:italic><jats:sub>KPC<\/jats:sub>.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>We report the mutated <jats:italic>bla<\/jats:italic><jats:sub>KPC<\/jats:sub> is not the only mechanism related to CZA resistance, and investigate the role of outer porin defects, efflux pump, and relative gene expression and copy number of <jats:italic>bla<\/jats:italic><jats:sub>KPC<\/jats:sub> and <jats:italic>ompk35\/36<\/jats:italic>. Four ceftazidime\/avibactam-sensitive isolates detected wild type <jats:italic>bla<\/jats:italic><jats:sub>KPC-2<\/jats:sub>, while 4 ceftazidime\/avibactam-resistant isolates detected mutated <jats:italic>bla<\/jats:italic><jats:sub>KPC<\/jats:sub> (<jats:italic>bla<\/jats:italic><jats:sub>KPC-51<\/jats:sub>, <jats:italic>bla<\/jats:italic><jats:sub>KPC-52<\/jats:sub>, and <jats:italic>bla<\/jats:italic><jats:sub>KPC-33<\/jats:sub>). Compared with other ceftazidime\/avibactam-resistant isolates with the minimal inhibitory concentration of ceftazidime\/avibactam ranging 128\u2013256\u2009mg\/L, the relative gene expression and copy number of <jats:italic>bla<\/jats:italic><jats:sub>KPC<\/jats:sub> was increased in the isolate which carried <jats:italic>bla<\/jats:italic><jats:sub>KPC-51<\/jats:sub> and also showed the highest minimal inhibitory concentration of ceftazidime\/avibactam at 2048\u2009mg\/L. The truncated Ompk35 contributes rare to ceftazidime\/avibactam resistance in our isolates. No significant difference in minimal inhibitory concentration of ceftazidime\/avibactam was observed after the addition of PABN.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Increased gene expression and copy number of mutated <jats:italic>bla<\/jats:italic><jats:sub>KPC<\/jats:sub> can cause high-level ceftazidime\/avibactam resistance.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12866-021-02293-0","type":"journal-article","created":{"date-parts":[[2021,8,19]],"date-time":"2021-08-19T10:08:42Z","timestamp":1629367722000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Increased gene expression and copy number of mutated blaKPC lead to high-level ceftazidime\/avibactam resistance in Klebsiella pneumoniae"],"prefix":"10.1186","volume":"21","author":[{"given":"Lingxiao","family":"Sun","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haibo","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingmei","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,8,19]]},"reference":[{"key":"2293_CR1","doi-asserted-by":"crossref","unstructured":"Zhang Y, Wang Q, Yin Y, Chen H, Jin L, Gu B, et al. Epidemiology of carbapenem-resistant enterobacteriaceae infections: report from the China CRE network. Antimicrob Agents Chemother. 2018;62(2):e01882\u201317.","DOI":"10.1128\/AAC.01882-17"},{"issue":"2","key":"2293_CR2","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1093\/cid\/ciw243","volume":"63","author":"D van Duin","year":"2016","unstructured":"van Duin D, Bonomo RA. Ceftazidime\/avibactam and Ceftolozane\/Tazobactam: second-generation beta-lactam\/beta-lactamase inhibitor combinations. Clin Infect Dis. 2016;63(2):234\u201341. https:\/\/doi.org\/10.1093\/cid\/ciw243.","journal-title":"Clin Infect Dis"},{"issue":"12","key":"2293_CR3","doi-asserted-by":"publisher","first-page":"1615","DOI":"10.1093\/cid\/ciw636","volume":"63","author":"RK Shields","year":"2016","unstructured":"Shields RK, Potoski BA, Haidar G, Hao B, Doi Y, Chen L, et al. Clinical outcomes, drug toxicity, and emergence of ceftazidime-avibactam resistance among patients treated for Carbapenem-resistant Enterobacteriaceae infections. Clin Infect Dis. 2016;63(12):1615\u20138. https:\/\/doi.org\/10.1093\/cid\/ciw636.","journal-title":"Clin Infect Dis"},{"key":"2293_CR4","doi-asserted-by":"crossref","unstructured":"Shields RK, Chen L, Cheng S, Chavda KD, Press EG, Snyder A, et al. Emergence of ceftazidime-avibactam resistance due to plasmid-borne blaKPC-3 mutations during treatment of carbapenem-resistant Klebsiella pneumoniae infections. Antimicrob Agents Chemother. 2017;61(3):e02097\u201316.","DOI":"10.1128\/AAC.02097-16"},{"issue":"3","key":"2293_CR5","doi-asserted-by":"publisher","first-page":"ofx101","DOI":"10.1093\/ofid\/ofx101","volume":"4","author":"RK Shields","year":"2017","unstructured":"Shields RK, Nguyen MH, Press EG, Chen L, Kreiswirth BN, Clancy CJ. Emergence of ceftazidime-avibactam resistance and restoration of carbapenem susceptibility in Klebsiella pneumoniae carbapenemase-producing K pneumoniae: a case report and review of literature. Open Forum Infect Dis. 2017;4(3):ofx101.","journal-title":"Open Forum Infect Dis"},{"key":"2293_CR6","doi-asserted-by":"crossref","unstructured":"Giddins MJ, Macesic N, Annavajhala MK, Stump S, Khan S, McConville TH, et al. Successive emergence of ceftazidime-avibactam resistance through distinct genomic adaptations in blaKPC-2-harboring Klebsiella pneumoniae sequence type 307 isolates. Antimicrob Agents Chemother. 2018;62(3):e02101\u201317.","DOI":"10.1128\/AAC.02101-17"},{"key":"2293_CR7","doi-asserted-by":"crossref","unstructured":"Athans V, Neuner EA, Hassouna H, Richter SS, Keller G, Castanheira M, et al. Meropenem-vaborbactam as salvage therapy for ceftazidime-avibactam-resistant Klebsiella pneumoniae bacteremia and abscess in a liver transplant recipient. Antimicrob Agents Chemother. 2019;63(1):e01551\u201318.","DOI":"10.1128\/AAC.01551-18"},{"issue":"5","key":"2293_CR8","doi-asserted-by":"publisher","first-page":"1241","DOI":"10.1093\/jac\/dkz026","volume":"74","author":"P Hemarajata","year":"2019","unstructured":"Hemarajata P, Humphries RM. Ceftazidime\/avibactam resistance associated with L169P mutation in the omega loop of KPC-2. J Antimicrob Chemother. 2019;74(5):1241\u20133. https:\/\/doi.org\/10.1093\/jac\/dkz026.","journal-title":"J Antimicrob Chemother"},{"issue":"6","key":"2293_CR9","doi-asserted-by":"publisher","first-page":"1525","DOI":"10.1093\/jac\/dky082","volume":"73","author":"P Gaibani","year":"2018","unstructured":"Gaibani P, Campoli C, Lewis RE, Volpe SL, Scaltriti E, Giannella M, et al. In vivo evolution of resistant subpopulations of KPC-producing Klebsiella pneumoniae during ceftazidime\/avibactam treatment. J Antimicrob Chemother. 2018;73(6):1525\u20139. https:\/\/doi.org\/10.1093\/jac\/dky082.","journal-title":"J Antimicrob Chemother"},{"key":"2293_CR10","doi-asserted-by":"crossref","unstructured":"Raisanen K, Koivula I, Ilmavirta H, Puranen S, Kallonen T, Lyytikainen O, et al. Emergence of ceftazidime-avibactam-resistant Klebsiella pneumoniae during treatment, Finland december 2018. Euro Surveill. 2019;24(19):1900256.","DOI":"10.2807\/1560-7917.ES.2019.24.19.1900256"},{"key":"2293_CR11","doi-asserted-by":"publisher","first-page":"1935","DOI":"10.2147\/IDR.S207993","volume":"12","author":"C Venditti","year":"2019","unstructured":"Venditti C, Nisii C, D'Arezzo S, Vulcano A, Capone A, Antonini M, et al. Molecular and phenotypical characterization of two cases of antibiotic-driven ceftazidime-avibactam resistance in Bla KPC-3-harboring Klebsiella pneumoniae. Infect Drug Resist. 2019;12:1935\u201340. https:\/\/doi.org\/10.2147\/IDR.S207993.","journal-title":"Infect Drug Resist"},{"issue":"11","key":"2293_CR12","doi-asserted-by":"publisher","first-page":"3211","DOI":"10.1093\/jac\/dkz330","volume":"74","author":"S Gottig","year":"2019","unstructured":"Gottig S, Frank D, Mungo E, Nolte A, Hogardt M, Besier S, et al. Emergence of ceftazidime\/avibactam resistance in KPC-3-producing Klebsiella pneumoniae in vivo. J Antimicrob Chemother. 2019;74(11):3211\u20136. https:\/\/doi.org\/10.1093\/jac\/dkz330.","journal-title":"J Antimicrob Chemother"},{"key":"2293_CR13","doi-asserted-by":"crossref","unstructured":"Shields RK, Nguyen MH, Chen L, Press EG, Kreiswirth BN, Clancy CJ. Pneumonia and renal replacement therapy are risk factors for ceftazidime-avibactam treatment failures and resistance among patients with carbapenem-resistant enterobacteriaceae infections. Antimicrob Agents Chemother. 2018;62(5):e02497\u201317.","DOI":"10.1128\/AAC.02497-17"},{"key":"2293_CR14","doi-asserted-by":"crossref","unstructured":"Mueller L, Masseron A, Prod'Hom G, Galperine T, Greub G, Poirel L, et al. Phenotypic, biochemical and genetic analysis of KPC-41, a KPC-3 variant conferring resistance to ceftazidime-avibactam and exhibiting reduced carbapenemase activity. Antimicrob Agents Chemother. 2019;63(12):e01111\u201319.","DOI":"10.1128\/AAC.01111-19"},{"issue":"1","key":"2293_CR15","doi-asserted-by":"publisher","first-page":"105816","DOI":"10.1016\/j.ijantimicag.2019.09.020","volume":"55","author":"P Gaibani","year":"2020","unstructured":"Gaibani P, Ambretti S, Campoli C, Viale P, Re MC. Genomic characterization of a Klebsiella pneumoniae ST1519 resistant to ceftazidime\/avibactam carrying a novel KPC variant (KPC-36). Int J Antimicrob Agents. 2020;55(1):105816. https:\/\/doi.org\/10.1016\/j.ijantimicag.2019.09.020.","journal-title":"Int J Antimicrob Agents"},{"issue":"8","key":"2293_CR16","doi-asserted-by":"publisher","first-page":"2464","DOI":"10.1093\/jac\/dkz156","volume":"74","author":"A Antonelli","year":"2019","unstructured":"Antonelli A, Giani T, Di Pilato V, Riccobono E, Perriello G, Mencacci A, et al. KPC-31 expressed in a ceftazidime\/avibactam-resistant Klebsiella pneumoniae is associated with relevant detection issues. J Antimicrob Chemother. 2019;74(8):2464\u20136. https:\/\/doi.org\/10.1093\/jac\/dkz156.","journal-title":"J Antimicrob Chemother"},{"issue":"9","key":"2293_CR17","doi-asserted-by":"publisher","first-page":"2483","DOI":"10.1093\/jac\/dkx179","volume":"72","author":"A Both","year":"2017","unstructured":"Both A, Buttner H, Huang J, Perbandt M, Belmar Campos C, Christner M, et al. Emergence of ceftazidime\/avibactam non-susceptibility in an MDR Klebsiella pneumoniae isolate. J Antimicrob Chemother. 2017;72(9):2483\u20138. https:\/\/doi.org\/10.1093\/jac\/dkx179.","journal-title":"J Antimicrob Chemother"},{"issue":"10","key":"2293_CR18","doi-asserted-by":"publisher","first-page":"6605","DOI":"10.1128\/AAC.01165-15","volume":"59","author":"RM Humphries","year":"2015","unstructured":"Humphries RM, Yang S, Hemarajata P, Ward KW, Hindler JA, Miller SA, et al. First report of ceftazidime-avibactam resistance in a KPC-3-expressing Klebsiella pneumoniae isolate. Antimicrob Agents Chemother. 2015;59(10):6605\u20137. https:\/\/doi.org\/10.1128\/AAC.01165-15.","journal-title":"Antimicrob Agents Chemother"},{"issue":"7","key":"2293_CR19","doi-asserted-by":"publisher","first-page":"1930","DOI":"10.1093\/jac\/dkx066","volume":"72","author":"Z Shen","year":"2017","unstructured":"Shen Z, Ding B, Ye M, Wang P, Bi Y, Wu S, et al. High ceftazidime hydrolysis activity and porin OmpK35 deficiency contribute to the decreased susceptibility to ceftazidime\/avibactam in KPC-producing Klebsiella pneumoniae. J Antimicrob Chemother. 2017;72(7):1930\u20136. https:\/\/doi.org\/10.1093\/jac\/dkx066.","journal-title":"J Antimicrob Chemother"},{"issue":"6","key":"2293_CR20","doi-asserted-by":"publisher","first-page":"763 e765","DOI":"10.1016\/j.cmi.2019.03.011","volume":"25","author":"I Galani","year":"2019","unstructured":"Galani I, Antoniadou A, Karaiskos I, Kontopoulou K, Giamarellou H, Souli M. Genomic characterization of a KPC-23-producing Klebsiella pneumoniae ST258 clinical isolate resistant to ceftazidime-avibactam. Clin Microbiol Infect. 2019;25(6):763 e765\u20138.","journal-title":"Clin Microbiol Infect"},{"key":"2293_CR21","doi-asserted-by":"crossref","unstructured":"Humphries RM, Hemarajata P. Resistance to ceftazidime-avibactam in Klebsiella pneumoniae due to porin mutations and the increased expression of KPC-3. Antimicrob Agents Chemother. 2017;61(6):e00537\u201317.","DOI":"10.1128\/AAC.00537-17"},{"key":"2293_CR22","doi-asserted-by":"crossref","unstructured":"Nelson K, Hemarajata P, Sun D, Rubio-Aparicio D, Tsivkovski R, Yang S, et al. Resistance to ceftazidime-avibactam is due to transposition of KPC in a porin-deficient strain of Klebsiella pneumoniae with increased efflux activity. Antimicrob Agents Chemother. 2017;61(10):e00989\u201317.","DOI":"10.1128\/AAC.00989-17"},{"issue":"1","key":"2293_CR23","doi-asserted-by":"publisher","first-page":"124 e121","DOI":"10.1016\/j.cmi.2019.08.020","volume":"26","author":"P Zhang","year":"2020","unstructured":"Zhang P, Shi Q, Hu H, Hong B, Wu X, Du X, et al. Emergence of ceftazidime\/avibactam resistance in carbapenem-resistant Klebsiella pneumoniae in China. Clin Microbiol Infect. 2020;26(1):124 e121\u20134.","journal-title":"Clin Microbiol Infect"},{"issue":"3","key":"2293_CR24","doi-asserted-by":"publisher","first-page":"39","DOI":"10.21037\/atm.2019.10.40","volume":"8","author":"W Chen","year":"2020","unstructured":"Chen W, Sun L, Guo L, Cao B, Liu Y, Zhao L, et al. Clinical outcomes of ceftazidime-avibactam in lung transplant recipients with infections caused by extensively drug-resistant gram-negative bacilli. Ann Transl Med. 2020;8(3):39. https:\/\/doi.org\/10.21037\/atm.2019.10.40.","journal-title":"Ann Transl Med"},{"issue":"10","key":"2293_CR25","doi-asserted-by":"publisher","first-page":"3072","DOI":"10.1093\/jac\/dkaa241","volume":"75","author":"L Sun","year":"2020","unstructured":"Sun L, Chen W, Li H, Li L, Zou X, Zhao J, et al. Phenotypic and genotypic analysis of KPC-51 and KPC-52, two novel KPC-2 variants conferring resistance to ceftazidime\/avibactam in the KPC-producing Klebsiella pneumoniae ST11 clone background. J Antimicrob Chemother. 2020;75(10):3072\u20134. https:\/\/doi.org\/10.1093\/jac\/dkaa241.","journal-title":"J Antimicrob Chemother"},{"key":"2293_CR26","doi-asserted-by":"crossref","unstructured":"Coppi M, Di Pilato V, Monaco F, Giani T, Conaldi PG, Rossolini GM. Ceftazidime-avibactam resistance associated with increased bla KPC-3 gene copy number mediated by pKpQIL Plasmid derivatives in sequence type 258 Klebsiella pneumoniae. Antimicrob Agents Chemother. 2020;64(4):e01816\u201319.","DOI":"10.1128\/AAC.01816-19"},{"issue":"1","key":"2293_CR27","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1007\/s10096-020-04000-9","volume":"40","author":"I Galani","year":"2021","unstructured":"Galani I, Karaiskos I, Angelidis E, Papoutsaki V, Galani L, Souli M, et al. Emergence of ceftazidime-avibactam resistance through distinct genomic adaptations in KPC-2-producing Klebsiella pneumoniae of sequence type 39 during treatment. Eur J Clin Microbiol Infect Dis. 2021;40(1):219\u201324. https:\/\/doi.org\/10.1007\/s10096-020-04000-9.","journal-title":"Eur J Clin Microbiol Infect Dis"},{"key":"2293_CR28","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.jgar.2019.11.007","volume":"22","author":"A Cano","year":"2020","unstructured":"Cano A, Guzman-Puche J, Garcia-Gutierrez M, Caston JJ, Gracia-Ahufinger I, Perez-Nadales E, et al. Use of carbapenems in the combined treatment of emerging ceftazidime\/avibactam-resistant and carbapenem-susceptible KPC-producing Klebsiella pneumoniae infections: report of a case and review of the literature. J Glob Antimicrob Resist. 2020;22:9\u201312. https:\/\/doi.org\/10.1016\/j.jgar.2019.11.007.","journal-title":"J Glob Antimicrob Resist"},{"issue":"4","key":"2293_CR29","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1089\/mdr.2016.0017","volume":"23","author":"L Pulzova","year":"2017","unstructured":"Pulzova L, Navratilova L, Comor L. Alterations in outer membrane permeability favor drug-resistant phenotype of Klebsiella pneumoniae. Microb Drug Resist. 2017;23(4):413\u201320. https:\/\/doi.org\/10.1089\/mdr.2016.0017.","journal-title":"Microb Drug Resist"},{"issue":"1","key":"2293_CR30","doi-asserted-by":"publisher","first-page":"3957","DOI":"10.1038\/s41467-019-11756-y","volume":"10","author":"JLC Wong","year":"2019","unstructured":"Wong JLC, Romano M, Kerry LE, Kwong HS, Low WW, Brett SJ, et al. OmpK36-mediated Carbapenem resistance attenuates ST258 Klebsiella pneumoniae in vivo. Nat Commun. 2019;10(1):3957. https:\/\/doi.org\/10.1038\/s41467-019-11756-y.","journal-title":"Nat Commun"},{"key":"2293_CR31","doi-asserted-by":"crossref","unstructured":"Castanheira M, Mendes RE, Sader HS. Low frequency of ceftazidime-avibactam resistance among enterobacteriaceae isolates carrying blaKPC Collected in U.S. hospitals from 2012 to 2015. Antimicrob Agents Chemother. 2017;61(3):e02369\u201316.","DOI":"10.1128\/AAC.02369-16"},{"issue":"9","key":"2293_CR32","doi-asserted-by":"publisher","first-page":"5793","DOI":"10.1128\/AAC.00548-15","volume":"59","author":"RK Shields","year":"2015","unstructured":"Shields RK, Clancy CJ, Hao B, Chen L, Press EG, Iovine NM, et al. Effects of Klebsiella pneumoniae carbapenemase subtypes, extended-spectrum beta-lactamases, and porin mutations on the in vitro activity of ceftazidime-avibactam against carbapenem-resistant K. pneumoniae. Antimicrob Agents Chemother. 2015;59(9):5793\u20137. https:\/\/doi.org\/10.1128\/AAC.00548-15.","journal-title":"Antimicrob Agents Chemother"},{"key":"2293_CR33","doi-asserted-by":"publisher","first-page":"1365","DOI":"10.3389\/fmicb.2020.01365","volume":"11","author":"X Cui","year":"2020","unstructured":"Cui X, Shan B, Zhang X, Qu F, Jia W, Huang B, et al. Reduced ceftazidime-avibactam susceptibility in KPC-producing Klebsiella pneumoniae from patients without ceftazidime-avibactam use history - a multicenter study in China. Front Microbiol. 2020;11:1365. https:\/\/doi.org\/10.3389\/fmicb.2020.01365.","journal-title":"Front Microbiol"},{"key":"2293_CR34","doi-asserted-by":"crossref","unstructured":"Di Pilato V, Aiezza N, Viaggi V, Antonelli A, Principe L, Giani T, et al. KPC-53, a KPC-3 variant of clinical origin associated with reduced susceptibility to ceftazidime-avibactam. Antimicrob Agents Chemother. 2020:65(1):e01429\u201320.","DOI":"10.1128\/AAC.01429-20"},{"issue":"7","key":"2293_CR35","doi-asserted-by":"publisher","first-page":"e42280","DOI":"10.1371\/journal.pone.0042280","volume":"7","author":"B Li","year":"2012","unstructured":"Li B, Yi Y, Wang Q, Woo PC, Tan L, Jing H, et al. Analysis of drug resistance determinants in Klebsiella pneumoniae isolates from a tertiary-care hospital in Beijing, China. PLoS One. 2012;7(7):e42280. https:\/\/doi.org\/10.1371\/journal.pone.0042280.","journal-title":"PLoS One"},{"issue":"4","key":"2293_CR36","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1093\/jac\/dkp029","volume":"63","author":"M Doumith","year":"2009","unstructured":"Doumith M, Ellington MJ, Livermore DM, Woodford N. Molecular mechanisms disrupting porin expression in ertapenem-resistant Klebsiella and Enterobacter spp. clinical isolates from the UK. J Antimicrob Chemother. 2009;63(4):659\u201367. https:\/\/doi.org\/10.1093\/jac\/dkp029.","journal-title":"J Antimicrob Chemother"},{"issue":"3","key":"2293_CR37","doi-asserted-by":"publisher","first-page":"1017","DOI":"10.1128\/AAC.49.3.1017-1022.2005","volume":"49","author":"A Ruzin","year":"2005","unstructured":"Ruzin A, Visalli MA, Keeney D, Bradford PA. Influence of transcriptional activator RamA on expression of multidrug efflux pump AcrAB and tigecycline susceptibility in Klebsiella pneumoniae. Antimicrob Agents Chemother. 2005;49(3):1017\u201322. https:\/\/doi.org\/10.1128\/AAC.49.3.1017-1022.2005.","journal-title":"Antimicrob Agents Chemother"},{"issue":"10","key":"2293_CR38","doi-asserted-by":"publisher","first-page":"4201","DOI":"10.1128\/AAC.00008-10","volume":"54","author":"B Kitchel","year":"2010","unstructured":"Kitchel B, Rasheed JK, Endimiani A, Hujer AM, Anderson KF, Bonomo RA, et al. Genetic factors associated with elevated carbapenem resistance in KPC-producing Klebsiella pneumoniae. Antimicrob Agents Chemother. 2010;54(10):4201\u20137. https:\/\/doi.org\/10.1128\/AAC.00008-10.","journal-title":"Antimicrob Agents Chemother"},{"key":"2293_CR39","doi-asserted-by":"crossref","unstructured":"Wang Y, Wang S, Chen W, Song L, Zhang Y, Shen Z, et al. CRISPR-Cas9 and CRISPR-assisted cytidine deaminase enable precise and efficient genome editing in Klebsiella pneumoniae. Appl Environ Microbiol. 2018;84(23):e01834\u201318.","DOI":"10.1128\/AEM.01834-18"},{"issue":"3","key":"2293_CR40","doi-asserted-by":"publisher","first-page":"330","DOI":"10.1128\/jcm.24.3.330-332.1986","volume":"24","author":"GM Carlone","year":"1986","unstructured":"Carlone GM, Thomas ML, Rumschlag HS, Sottnek FO. Rapid microprocedure for isolating detergent-insoluble outer membrane proteins from Haemophilus species. J Clin Microbiol. 1986;24(3):330\u20132. https:\/\/doi.org\/10.1128\/jcm.24.3.330-332.1986.","journal-title":"J Clin Microbiol"},{"issue":"2","key":"2293_CR41","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1128\/CMR.00117-14","volume":"28","author":"XZ Li","year":"2015","unstructured":"Li XZ, Plesiat P, Nikaido H. The challenge of efflux-mediated antibiotic resistance in gram-negative bacteria. Clin Microbiol Rev. 2015;28(2):337\u2013418. https:\/\/doi.org\/10.1128\/CMR.00117-14.","journal-title":"Clin Microbiol Rev"},{"issue":"1","key":"2293_CR42","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1093\/molbev\/msu300","volume":"32","author":"LT Nguyen","year":"2015","unstructured":"Nguyen LT, Schmidt HA, von Haeseler A, Minh BQ. IQ-TREE: a fast and effective stochastic algorithm for estimating maximum-likelihood phylogenies. Mol Biol Evol. 2015;32(1):268\u201374. https:\/\/doi.org\/10.1093\/molbev\/msu300.","journal-title":"Mol Biol Evol"},{"issue":"2","key":"2293_CR43","doi-asserted-by":"publisher","first-page":"518","DOI":"10.1093\/molbev\/msx281","volume":"35","author":"DT Hoang","year":"2018","unstructured":"Hoang DT, Chernomor O, von Haeseler A, Minh BQ, Vinh LS. UFBoot2: improving the ultrafast bootstrap approximation. Mol Biol Evol. 2018;35(2):518\u201322. https:\/\/doi.org\/10.1093\/molbev\/msx281.","journal-title":"Mol Biol Evol"}],"container-title":["BMC Microbiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12866-021-02293-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12866-021-02293-0\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12866-021-02293-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,8,19]],"date-time":"2021-08-19T10:13:48Z","timestamp":1629368028000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcmicrobiol.biomedcentral.com\/articles\/10.1186\/s12866-021-02293-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,19]]},"references-count":43,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["2293"],"URL":"https:\/\/doi.org\/10.1186\/s12866-021-02293-0","relation":{},"ISSN":["1471-2180"],"issn-type":[{"value":"1471-2180","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,19]]},"assertion":[{"value":"28 February 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 August 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 August 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Permission for using the raw data and the isolates for research purposes was approved by the Ethics Committee of the China-Japan Friendship Hospital (2019\u2013164-K113). Because of the retrospective nature of this study, informed consent is not needed. The data used in this study was anonymised before its use.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"230"}}