{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T01:06:04Z","timestamp":1792026364112,"version":"4.4.0"},"reference-count":67,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2023,6,27]],"date-time":"2023-06-27T00:00:00Z","timestamp":1687824000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI 17\/02241"],"award-info":[{"award-number":["PI 17\/02241"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Plan Nacional de I+D+i 2013\u20132016","award":["PI 17\/02241"],"award-info":[{"award-number":["PI 17\/02241"]}]},{"name":"Subdirecci\u00f3n General de Redes y Centros de Investigaci\u00f3n Cooperativa","award":["PI 17\/02241"],"award-info":[{"award-number":["PI 17\/02241"]}]},{"name":"Ministerio de Econom\u00eda y Competitividad","award":["PI 17\/02241"],"award-info":[{"award-number":["PI 17\/02241"]}]},{"name":"Spanish Network for Research in Infectious Diseases","award":["PI 17\/02241"],"award-info":[{"award-number":["PI 17\/02241"]}]},{"name":"European Development Regional Fund \u201cA way to achieve Europe\u201d Operative Program Intelligent Growth 2014\u20132020","award":["PI 17\/02241"],"award-info":[{"award-number":["PI 17\/02241"]}]},{"name":"pre-doctoral contract from the University of Cordoba, Spain","award":["PI 17\/02241"],"award-info":[{"award-number":["PI 17\/02241"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Heteroresistance to colistin can be defined as the presence of resistant subpopulations in an isolate that is susceptible to this antibiotic. Colistin resistance in Gram-negative bacteria is more frequently related to chromosomal mutations and insertions. This work aimed to study heteroresistance in nine clinical isolates of Klebsiella pneumoniae producing OXA-48 and to describe genomic changes in mutants with acquired resistance in vitro. Antimicrobial susceptibility was determined by broth microdilution (BMD) and heteroresistance by population analysis profiling (PAP). The proteins related to colistin resistance were analyzed for the presence of mutations. Additionally, PCR of the mgrB gene was performed to identify the presence of insertions. In the nine parental isolates, the PAP method showed colistin heteroresistance of colonies growing on plates with concentrations of up to 64 mg\/L, corresponding to stable mutant subpopulations. The MICs of some mutants from the PAP plate containing 4\u00d7MIC of colistin had absolute values of \u22642 mg\/L that were higher than the parental MICs and were defined as persistent variants. PCR of the mgrB gene identified an insertion sequence that inactivated the gene in 21 mutants. Other substitutions in the investigated mutants were found in PhoP, PhoQ, PmrB, PmrC, CrrA and CrrB proteins. Colistin heteroresistance in K. pneumoniae isolates was attributed mainly to insertions in the mgrB gene and point mutations in colistin resistance proteins. The results of this study will improve understanding regarding the mechanisms of colistin resistance in mutants of K. pneumoniae producing OXA-48.<\/jats:p>","DOI":"10.3390\/antibiotics12071111","type":"journal-article","created":{"date-parts":[[2023,6,28]],"date-time":"2023-06-28T00:25:21Z","timestamp":1687911921000},"page":"1111","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Heteroresistance to Colistin in Clinical Isolates of Klebsiella pneumoniae Producing OXA-48"],"prefix":"10.3390","volume":"12","author":[{"given":"Irene","family":"S\u00e1nchez-Le\u00f3n","sequence":"first","affiliation":[{"name":"Maimonides Biomedical Research Institute of Cordoba, 14004 Cordoba, Spain"},{"name":"Department of Agricultural Chemistry, Edaphology and Microbiology, Agrifood Campus of International Excellence CeiA3, University of Cordoba, 14014 Cordoba, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2746-2753","authenticated-orcid":false,"given":"Teresa","family":"Garc\u00eda-Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Department of Agricultural Chemistry, Edaphology and Microbiology, Agrifood Campus of International Excellence CeiA3, University of Cordoba, 14014 Cordoba, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6466-2324","authenticated-orcid":false,"given":"Seydina M.","family":"Diene","sequence":"additional","affiliation":[{"name":"Microbes Evolution Phylogeny and Infections (MEPHI), IRD, APHM, IHU M\u00e9diterran\u00e9e Infection, Facult\u00e9 de M\u00e9decine et de Pharmacie, Aix-Marseille-University, 13005 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6796-1813","authenticated-orcid":false,"given":"Elena","family":"P\u00e9rez-Nadales","sequence":"additional","affiliation":[{"name":"Maimonides Biomedical Research Institute of Cordoba, 14004 Cordoba, Spain"},{"name":"Department of Agricultural Chemistry, Edaphology and Microbiology, Agrifood Campus of International Excellence CeiA3, University of Cordoba, 14014 Cordoba, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6091-4045","authenticated-orcid":false,"given":"Luis","family":"Mart\u00ednez-Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Maimonides Biomedical Research Institute of Cordoba, 14004 Cordoba, Spain"},{"name":"Department of Agricultural Chemistry, Edaphology and Microbiology, Agrifood Campus of International Excellence CeiA3, University of Cordoba, 14014 Cordoba, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, 28029 Madrid, Spain"},{"name":"Clinical Unit of Microbiology, Reina Sof\u00eda University Hospital, 14004 Cordoba, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Marc","family":"Rolain","sequence":"additional","affiliation":[{"name":"Microbes Evolution Phylogeny and Infections (MEPHI), IRD, APHM, IHU M\u00e9diterran\u00e9e Infection, Facult\u00e9 de M\u00e9decine et de Pharmacie, Aix-Marseille-University, 13005 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"895","DOI":"10.3389\/fmicb.2016.00895","article-title":"Global Dissemination of Carbapenemase-Producing Klebsiella pneumoniae: Epidemiology, Genetic Context, Treatment Options, and Detection Methods","volume":"7","author":"Lee","year":"2016","journal-title":"Front. 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