{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T13:13:43Z","timestamp":1791465223250,"version":"4.3.4"},"reference-count":47,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,7,27]],"date-time":"2017-07-27T00:00:00Z","timestamp":1501113600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,7,27]],"date-time":"2017-07-27T00:00:00Z","timestamp":1501113600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    <jats:italic>Klebsiella pneumoniae<\/jats:italic>\n                    , an Enterobacteriaceae that mostly causes hospital-acquired infections, belongs to the recently published WHO\u2019s list of antibiotic-resistant pathogens that pose the greatest threat to human health. Indeed,\n                    <jats:italic>K. pneumoniae<\/jats:italic>\n                    is the enterobacterial species most concerned by both resistance to extended-spectrum cephalosporins, due to extended-spectrum \u03b2-lactamase (ESBL) production, and resistance to carbapenems,\n                    <jats:italic>i.e<\/jats:italic>\n                    . the \u03b2-lactams with the broadest activity. Carbapenem resistance is related not only to carbapenemase production, but also the production of ESBL or AmpC and the loss of general porins. Here, we characterized the mechanisms that deprived a urinary ESBL-producing, porin-deficient\n                    <jats:italic>K. pneumoniae<\/jats:italic>\n                    isolate, isolated 13 days after the end of a 40-day course of imipenem treatment, of its carbapenem resistance. These mechanisms were observed in two\n                    <jats:italic>in-vivo<\/jats:italic>\n                    derivatives of this isolate and consisted of mutations in genes encoding molecules that participate in the downregulation of the synthesis of PhoE, a porin specialized in phosphate transport. We obtained three new derivatives from one of the two original derivatives, following\n                    <jats:italic>in-vitro<\/jats:italic>\n                    antibiotic pressure, in which the carbapenem resistance was restored because of mutations in genes encoding molecules that participate in the upregulation of PhoE synthesis. Thus, we uncovered novel mechanisms of carbapenem resistance\/susceptibility switching in\n                    <jats:italic>K. pneumoniae<\/jats:italic>\n                    .\n                  <\/jats:p>","DOI":"10.1038\/s41598-017-06503-6","type":"journal-article","created":{"date-parts":[[2017,7,21]],"date-time":"2017-07-21T09:49:59Z","timestamp":1500630599000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["In-vivo loss of carbapenem resistance by extensively drug-resistant Klebsiella pneumoniae during treatment via porin expression modification"],"prefix":"10.1038","volume":"7","author":[{"given":"Suzanne","family":"Bialek-Davenet","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"No\u00e9mie","family":"Mayer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Vergalli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marion","family":"Duprilot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvain","family":"Brisse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7092-7977","authenticated-orcid":false,"given":"Jean-Marie","family":"Pag\u00e8s","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-H\u00e9l\u00e8ne","family":"Nicolas-Chanoine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,7,27]]},"reference":[{"key":"6503_CR1","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1128\/CMR.11.4.589","volume":"11","author":"R Podschun","year":"1998","unstructured":"Podschun, R. & Ullmann, U. Klebsiella spp. as nosocomial pathogens: Epidemiology, taxonomy, typing methods, and pathogenicity factors. Clin Microbiol Rev \n                           11, 589\u2013603 (1998).","journal-title":"Clin Microbiol Rev"},{"key":"6503_CR2","first-page":"e01976","volume":"8","author":"D Moradigaravand","year":"2017","unstructured":"Moradigaravand, D., Martin, V., Sharon, P. & Parkhill, J. Evolution and epidemiology of multidrug-resistant Klebsiella pneumoniae in the United Kingdom and Ireland. MBio \n                           8, e01976\u201301916 (2017).","journal-title":"MBio"},{"key":"6503_CR3","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1586\/eri.13.12","volume":"11","author":"J-N Pendleton","year":"2013","unstructured":"Pendleton, J.-N., Gorman, S.-P. & Gilmore, B.-F. Clinical relevance of the ESKAPE pathogens. Expert Rev Anti-Infect Ther \n                           11, 297\u2013308 (2013).","journal-title":"Expert Rev Anti-Infect Ther"},{"key":"6503_CR4","doi-asserted-by":"publisher","first-page":"1111","DOI":"10.1099\/jmm.0.000338","volume":"65","author":"J Du","year":"2016","unstructured":"Du, J. et al. Molecular epidemiology of extensively drug-resistant Klebsiella pneumoniae outbreak in Wenzhou, Southern China. J Med Microbiol \n                           65, 1111\u20131118 (2016).","journal-title":"J Med Microbiol"},{"key":"6503_CR5","doi-asserted-by":"publisher","first-page":"5873","DOI":"10.1128\/AAC.01019-15","volume":"59","author":"J-D Pitout","year":"2015","unstructured":"Pitout, J.-D., Nordmann, P. & Poirel, L. Carbapenemase-producing Klebsiella pneumoniae, a key pathogen set for global nosocomial dominance. 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Antimicrob Agents Chemother \n                           58, 3895\u20133903 (2014).","journal-title":"Antimicrob Agents Chemother"},{"key":"6503_CR22","doi-asserted-by":"publisher","first-page":"2795","DOI":"10.1128\/AAC.00156-11","volume":"55","author":"S Bialek-Davenet","year":"2011","unstructured":"Bialek-Davenet, S. et al. In vitro selection of ramR and soxR mutants overexpressing efflux systems by fluoroquinolones as well as cefoxitin in Klebsiella pneumoniae. Antimicrob Agents Chemother \n                           55, 2795\u20132802 (2011).","journal-title":"Antimicrob Agents Chemother"},{"key":"6503_CR23","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1093\/jac\/dku340","volume":"70","author":"S Bialek-Davenet","year":"2015","unstructured":"Bialek-Davenet, S. et al. Differential contribution of AcrAB and OqxAB efflux pumps to multidrug resistance and virulence in Klebsiella pneumoniae. 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Antimicrob Agents Chemother \n                           58, 1707\u20131712 (2014).","journal-title":"Antimicrob Agents Chemother"},{"key":"6503_CR30","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1111\/j.1574-6976.2008.00101.x","volume":"32","author":"MG Lamarche","year":"2008","unstructured":"Lamarche, M. G., Wanner, B. L., Crepin, S. & Harel, J. The phosphate regulon and bacterial virulence: a regulatory network connecting phosphate homeostasis and pathogenesis. FEMS Microbiol. Rev. \n                           32, 461\u2013473 (2008).","journal-title":"FEMS Microbiol. Rev."},{"key":"6503_CR31","doi-asserted-by":"publisher","first-page":"1741","DOI":"10.1128\/JB.00029-14","volume":"196","author":"S-G Gardner","year":"2014","unstructured":"Gardner, S.-G., Johns, K.-D., Tanner, R. & McCleary, W.-R. The PhoU protein from Escherichia coli interacts with PhoR, PstB, and metals to form a phosphate-signaling complex at the membrane. 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J Med Microbiol \n                           59, 115\u2013119 (2010).","journal-title":"J Med Microbiol"},{"key":"6503_CR36","doi-asserted-by":"publisher","first-page":"969","DOI":"10.1128\/JCM.00651-08","volume":"47","author":"A Leavitt","year":"2009","unstructured":"Leavitt, A. et al. Ertapenem resistance among extended-spectrum-\u03b2-lactamase-producing Klebsiella pneumoniae isolates. J Clin Microbiol \n                           47, 969\u2013974 (2009).","journal-title":"J Clin Microbiol"},{"key":"6503_CR37","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1093\/jac\/dkp029","volume":"63","author":"M Doumith","year":"2009","unstructured":"Doumith, M., Ellington, M. J., Livermore, D. M. & Woodford, N. Molecular mechanisms disrupting porin expression in ertapenem-resistant Klebsiella and Enterobacter spp. clinical isolates from the UK. 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Journal of global antimicrobial resistance \n                           7, 67\u201368 (2016).","journal-title":"Journal of global antimicrobial resistance"},{"key":"6503_CR40","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1016\/j.jgar.2016.12.011","volume":"9","author":"G Horna","year":"2017","unstructured":"Horna, G., Velasquez, J., Fernandez, N., Tamariz, J. & Ruiz, J. Characterization of the first KPC-2-producing Klebsiella pneumoniae ST340 in Peru. Journal of Global Antimicrobial Resistance \n                           9, 36\u201340 (2017).","journal-title":"Journal of Global Antimicrobial Resistance"},{"key":"6503_CR41","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1016\/j.diagmicrobio.2015.09.003","volume":"83","author":"WM Martin","year":"2015","unstructured":"Martin, W. M. et al. Coproduction of KPC-2 and QnrB19 in Klebsiella pneumoniae ST340 isolate in Brazil. Diagn Microbiol Infect Dis \n                           83, 375\u2013376 (2015).","journal-title":"Diagn Microbiol Infect Dis"},{"key":"6503_CR42","doi-asserted-by":"publisher","first-page":"2610","DOI":"10.1128\/AAC.02610-16","volume":"61","author":"G Peirano","year":"2017","unstructured":"Peirano, G. et al. The importance of clonal complex 258 and IncFK2-like plasmids among a global collection of Klebsiella pneumoniae with bla\n                           KPCs. Antimicrob Agents Chemother \n                           61, 2610\u20132616 (2017).","journal-title":"Antimicrob Agents Chemother"},{"key":"6503_CR43","first-page":"S2","volume":"16","author":"SG Gardner","year":"2015","unstructured":"Gardner, S. G. et al. Genetic analysis, structural modeling, and direct coupling analysis suggest a mechanism for phosphate signaling in Escherichia coli. 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