{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T12:56:29Z","timestamp":1777899389774,"version":"3.51.4"},"reference-count":47,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Higher Education and Scientific Research of Tunisia"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Infectious Disease Reports"],"abstract":"<jats:p>Background\/Objectives: Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a major nosocomial pathogen. Although newer agents have reduced colistin use in high-income countries, this polymyxin remains important in many low- and middle-income settings. Colistin resistance in K. pneumoniae is most commonly associated with chromosomal alterations affecting the MgrB\u2013PhoPQ pathway, or with plasmid-mediated mcr genes. This study aimed to investigate chromosomally mediated colistin resistance in CRKP clinical isolates from a Tunisian tertiary hospital. Methods: Between 2010 and 2015, 317 non-duplicate CRKP isolates were collected at Charles Nicolle Hospital, Tunis. Colistin MICs were determined by broth microdilution. Phenotypic tests and PCR characterized carbapenemases, extended-spectrum \u03b2-lactamases, AmpC, plasmid-mediated quinolone resistance, mcr and virulence genes. Porins (OmpK35\/OmpK36) and the mgrB, phoP and phoQ loci were analyzed by SDS-PAGE and sequencing. Clonal relatedness was assessed by ERIC-PCR and multilocus sequence typing. We additionally compared colistin-resistant isolates with a panel of colistin-susceptible CRKP controls and assessed phenotypic stability after serial passages without colistin. Results: Five isolates (1.6%) were colistin-resistant. All were multidrug-resistant, produced OXA-48, and two also carried NDM-1. The isolates belonged to five distinct sequence types, including high-risk clones (ST11, ST101, ST147). No mcr genes were detected. Four isolates carried disruptive mutations in mgrB, and the remaining strain harbored inactivating mutations in both phoP and phoQ with an intact mgrB. Truncating alterations in PhoP\/PhoQ and frequent loss or truncation of OmpK35\/OmpK36 were observed. No mgrB\/phoP\/phoQ alterations were detected among colistin-susceptible controls, and colistin MICs remained stable after 7 days of drug-free passaging. Conclusions: In Tunisian CRKP, colistin resistance was associated with chromosomal alterations, predominantly involving disruption of the MgrB\u2013PhoPQ pathway, in the absence of mcr genes. These mechanisms in both high-risk and emerging sequence types underscore the adaptability of CRKP and the need for surveillance where colistin remains an important therapeutic option.<\/jats:p>","DOI":"10.3390\/idr18030042","type":"journal-article","created":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T09:33:17Z","timestamp":1777627997000},"page":"42","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Chromosomal Mechanisms of Colistin Resistance in Clinical Isolates of Carbapenem-Resistant Klebsiella pneumoniae from a Tunisian Tertiary-Care Hospital"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8348-0000","authenticated-orcid":false,"given":"Zaineb","family":"Hamzaoui","sequence":"first","affiliation":[{"name":"LR99ES09, Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis 1007, Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0854-2344","authenticated-orcid":false,"given":"Hajer","family":"Kilani","sequence":"additional","affiliation":[{"name":"LR99ES09, Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis 1007, Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alain","family":"Ocampo-Sosa","sequence":"additional","affiliation":[{"name":"Microbiology Service, University Hospital Marqu\u00e9s de Valdecilla, 39008 Santander, Spain"},{"name":"Marqu\u00e9s de Valdecilla Research Institute (IDIVAL), 39008 Santander, Spain"},{"name":"Center for Biomedical Research in Infectious Diseases Network (CIBERINFEC), Instituto de Salud Carlos III, 28020 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sana","family":"Ferjani","sequence":"additional","affiliation":[{"name":"LR99ES09, Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis 1007, Tunisia"},{"name":"Laboratory of Microbiology, Charles Nicolle Hospital, Tunis 1006, Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0241-2191","authenticated-orcid":false,"given":"Elaa","family":"Maamar","sequence":"additional","affiliation":[{"name":"LR99ES09, Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis 1007, Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9594-3391","authenticated-orcid":false,"given":"Lamia","family":"Kanzari","sequence":"additional","affiliation":[{"name":"LR99ES09, Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis 1007, Tunisia"},{"name":"Laboratory of Microbiology, Charles Nicolle Hospital, Tunis 1006, Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ahmed","family":"Fakhfakh","sequence":"additional","affiliation":[{"name":"LR99ES09, Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis 1007, Tunisia"},{"name":"Laboratory of Microbiology, Charles Nicolle Hospital, Tunis 1006, Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amel","family":"Rehaiem","sequence":"additional","affiliation":[{"name":"LR99ES09, Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis 1007, Tunisia"},{"name":"Laboratory of Microbiology, Charles Nicolle Hospital, Tunis 1006, Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6091-4045","authenticated-orcid":false,"given":"Luis","family":"Mart\u00ednez-Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Center for Biomedical Research in Infectious Diseases Network (CIBERINFEC), Instituto de Salud Carlos III, 28020 Madrid, Spain"},{"name":"Maimonides Biomedical Research Institute of Cordoba (IMIBIC), 14004 Cordoba, Spain"},{"name":"Clinical Unit of Microbiology, University Hospital Reina Sof\u00eda, 14004 Cordoba, Spain"},{"name":"Department of Agricultural Chemistry, Soil Science and Microbiology (Microbiology Area), University of Cordoba, 14014 Cordoba, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ilhem","family":"Boutiba Ben Boubaker","sequence":"additional","affiliation":[{"name":"LR99ES09, Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis 1007, Tunisia"},{"name":"Laboratory of Microbiology, Charles Nicolle Hospital, Tunis 1006, Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"100246","DOI":"10.1016\/j.microb.2025.100246","article-title":"Carbapenem-Resistant Klebsiella pneumoniae: A Comprehensive Review of Phenotypic and Genotypic Methods for 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