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Chromosome-Mediated Colistin Resistance in Clinical Isolates of Klebsiella pneumoniae and Escherichia coli: Mutation Analysis in the Light of Genetic Background

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dc.contributor.authorRiquelme, María
dc.contributor.authorMartinez, Rodrigo
dc.contributor.authorBrito, Bárbara
dc.contributor.authorGarcía, Patricia
dc.contributor.authorLegarraga, Paulette
dc.contributor.authorWozniak, Aniela
dc.date.accessioned2024-05-08T20:38:59Z
dc.date.available2024-05-08T20:38:59Z
dc.date.issued2023
dc.description.abstractPurpose: Colistin resistance mechanisms involving mutations in chromosomal genes associated with LPS modification are not completely understood. Mutations in genes coding for the MgrB regulator frequently account for colistin resistance in Klebsiella pneumoniae, whereas mutations in genes coding for PhoPQ and PmrAB are frequent in E. coli. Our aim was to perform a genetic analysis of chromosomal mutations in colistin-resistant (MIC ≥4 µg/mL) clinical isolates of K. pneumoniae (n = 8) and E. coli (n = 7) of different STs. Methods: Isolates were obtained in a 3-year period in a university hospital in Santiago, Chile. Susceptibility to colistin, aminoglycosides, cephalosporins, carbapenems and ciprofloxacin was determined through broth microdilution. Whole genome sequencing was performed for all isolates and chromosomal gene sequences were compared with sequences of colistin-susceptible isolates of the same sequence types. Results: None of the isolates carried mcr genes. Most of the isolates were susceptible to all the antibiotics analyzed. E. coli isolates were ST69, ST127, ST59, ST131 and ST14, and K. pneumoniae isolates were ST454, ST45, ST6293, ST380 and ST25. All the isolates had mutations in chromosomal genes analyzed. K. pneumoniae had mutations mainly in mgrB gene, whereas E. coli had mutations in pmrA, pmrB and pmrE genes. Most of the amino acid changes in LPS-modifying enzymes of colistin-resistant isolates were found in colistin-susceptible isolates of the same and/or different ST. Eleven of them were found only in colistin-resistant isolates. Conclusion: Colistin resistance mechanisms depend on genetic background, and are due to chromosomal mutations, which implies a lower risk of transmission than plasmid-mediated genes. Colistin resistance is not associated with multidrug-resistance, nor to high-risk sequence types.
dc.description.versionPublicada
dc.identifier.citationRiquelme MP, Martinez RW, Brito B, García P, Legarraga P, Wozniak A. Chromosome-Mediated Colistin Resistance in Clinical Isolates of Klebsiella pneumoniae and Escherichia coli: Mutation Analysis in the Light of Genetic Background. Infect Drug Resist. 2023 Sep 28;16:6451-6462. doi: 10.2147/IDR.S427398
dc.identifier.doihttps://doi.org/10.2147/IDR.S427398
dc.identifier.urihttps://hdl.handle.net/11447/8727
dc.language.isoen
dc.subjectLPS-modifying enzymes
dc.subjectMgrB regulator
dc.subjectPmrA-PmrB and PhoP-PhoQ three-component systems
dc.subjectPolymorphism vs potential mutation
dc.subjectSequence type
dc.titleChromosome-Mediated Colistin Resistance in Clinical Isolates of Klebsiella pneumoniae and Escherichia coli: Mutation Analysis in the Light of Genetic Background
dc.typeArticle
dcterms.accessRightsAcceso Abierto
dcterms.sourceInfection and drug resistance
dspace.entity.typePublication

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