{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T12:57:37Z","timestamp":1790773057282,"version":"4.1.0"},"reference-count":26,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2020,1,20]],"date-time":"2020-01-20T00:00:00Z","timestamp":1579478400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100005297","name":"Medical University of Bialystok","doi-asserted-by":"publisher","award":["POPW.01.03.00\u201320-022\/09"],"award-info":[{"award-number":["POPW.01.03.00\u201320-022\/09"]}],"id":[{"id":"10.13039\/501100005297","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>The growing incidence of MDR Gram-negative bacteria is a rapidly emerging challenge in modern medicine.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>We sought to establish the role of intrinsic drug-resistance regulators in combination with specific genetic mutations in 11 Enterobacter cloacae isolates obtained from a single patient within a 7\u2009week period.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>The molecular characterization of eight carbapenem-resistant and three carbapenem-susceptible E. cloacae ST89 isolates included expression-level analysis and WGS. Quantitative PCR included: (i) chromosomal cephalosporinase gene (ampC); (ii) membrane permeability factor genes, e.g. ompF, ompC, acrA, acrB and tolC; and (iii) intrinsic regulatory genes, e.g. ramA, ampR, rob, marA and soxS, which confer reductions in antibiotic susceptibility.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>In this study we describe the influence of the alterations in membrane permeability (ompF and ompC levels), intrinsic regulatory genes (ramA, marA, soxS) and intrinsic chromosomal cephalosporinase AmpC on reductions in carbapenem susceptibility of E. cloacae clinical isolates. Interestingly, only the first isolate possessed the acquired VIM-4 carbapenemase, which has been lost in subsequent isolates. The remaining XDR E. cloacae ST89 isolates presented complex carbapenem-resistance pathways, which included perturbations in permeability of bacterial membranes mediated by overexpression of ramA, encoding an AraC\/XylS global regulator. Moreover, susceptible isolates differed significantly from other isolates in terms of marA down-regulation and soxS up-regulation.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Molecular mechanisms of resistance among carbapenem-resistant E. cloacae included production of acquired VIM-4 carbapenemase, significant alterations in membrane permeability due to increased expression of ramA, encoding an AraC\/XylS global regulator, and the overproduction of chromosomal AmpC cephalosporinase.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkz569","type":"journal-article","created":{"date-parts":[[2019,12,23]],"date-time":"2019-12-23T20:10:01Z","timestamp":1577131801000},"page":"1146-1150","source":"Crossref","is-referenced-by-count":11,"title":["Expression of AraC\/XylS stress response regulators in two distinct carbapenem-resistant Enterobacter cloacae ST89 biotypes"],"prefix":"10.1093","volume":"75","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3097-4581","authenticated-orcid":false,"given":"Piotr","family":"Majewski","sequence":"first","affiliation":[{"name":"Department of Microbiological Diagnostics and Infectious Immunology, Medical University of Bialystok, Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Gutowska","sequence":"first","affiliation":[{"name":"Department of Microbiological Diagnostics and Infectious Immunology, Medical University of Bialystok, Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pawel","family":"Sacha","sequence":"first","affiliation":[{"name":"Department of Microbiological Diagnostics and Infectious Immunology, Medical University of Bialystok, Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thamarai","family":"Schneiders","sequence":"first","affiliation":[{"name":"Infection Medicine, University of Edinburgh, Edinburgh, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariola","family":"Talalaj","sequence":"first","affiliation":[{"name":"Department of Anaesthesiology and Intensive Care with Postoperative Unit, University Children\u2019s Clinical Hospital, Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulina","family":"Majewska","sequence":"first","affiliation":[{"name":"Regional Centre for Transfusion Medicine, Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnieszka","family":"Zebrowska","sequence":"first","affiliation":[{"name":"Regional Centre for Transfusion Medicine, Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominika","family":"Ojdana","sequence":"first","affiliation":[{"name":"Department of Microbiological Diagnostics and Infectious Immunology, Medical University of Bialystok, Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piotr","family":"Wieczorek","sequence":"first","affiliation":[{"name":"Department of Microbiological Diagnostics and Infectious Immunology, Medical University of Bialystok, Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomasz","family":"Hauschild","sequence":"first","affiliation":[{"name":"Department of Microbiology, Institute of Biology, University of Bialystok, Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oksana","family":"Kowalczuk","sequence":"first","affiliation":[{"name":"Department of Clinical Molecular Biology, Medical University of Bialystok, Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacek","family":"Niklinski","sequence":"first","affiliation":[{"name":"Department of Clinical Molecular Biology, Medical University of Bialystok, Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piotr","family":"Radziwon","sequence":"first","affiliation":[{"name":"Regional Centre for Transfusion Medicine, Bialystok, Poland"},{"name":"Department of Hematology, Medical University of Bialystok, Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elzbieta","family":"Tryniszewska","sequence":"first","affiliation":[{"name":"Department of Microbiological Diagnostics and Infectious Immunology, Medical University of Bialystok, Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,1,20]]},"reference":[{"key":"2020042304561188600_dkz569-B1","doi-asserted-by":"crossref","first-page":"65","DOI":"10.3389\/fmicb.2011.00065","article-title":"Pseudomonas aeruginosa: resistance to the max","volume":"2","author":"Poole","year":"2011","journal-title":"Front 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