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A Phylogenomic Approach for the Analysis of Colistin Resistance-Associated Genes in Klebsiella Pneumoniae, its Mutational Diversity and Implications for Phenotypic Resistance

2022Journal article Open access
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dc.contributor.authorElias, R
dc.contributor.authorSpadar, A
dc.contributor.authorPhelan, J
dc.contributor.authorMelo-Cristino, J
dc.contributor.authorLito, L
dc.contributor.authorPinto, M
dc.contributor.authorGonçalves, L
dc.contributor.authorCampino, S
dc.contributor.authorClark, TG
dc.contributor.authorDuarte, A
dc.contributor.authorPerdigão, J
dc.date.accessioned2023-04-12T14:45:26Z
dc.date.available2023-04-12T14:45:26Z
dc.date.issued2022
dc.description.abstractThe emergence of carbapenemase-producing Klebsiella pneumoniae strains has triggered the use of old antibiotics such as colistin. This is driving the emergence of colistin resistance in multidrug-resistant strains that underlie life-threatening infections. This study analyses the mutational diversity of 22 genes associated with colistin resistance in 140 K. pneumoniae clinical isolates integrated in a high-resolution phylogenetic scenario. Colistin susceptibility was accessed by broth microdilution. A total of 98 isolates were susceptible and 16 were resistant, 10 of which were carbapenemase producers. Across the 22 genes examined, 171 non-synonymous mutations and 9 mutations associated with promoter regions were found. Eighty-five isolates had a truncation and/or deletion in at least one of the 22 genes. However, only seven mutations, the complete deletion of mgrB or insertion sequence (IS)-mediated disruption, were exclusively observed in resistant isolates. Four of these (mgrBIle13fs, pmrBGly207Asp, phoQHis339Asp and ramAIle28Met) comprised novel mutations that are potentially involved in colistin resistance. One strain bore a ISEcp1-blaCTX-M-15::mgrB disruption, underlying co-resistance to third-generation cephalosporins and colistin. Moreover, the high-resolution phylogenetic context shows that most of the mutational diversity spans multiple phylogenetic clades, and most of the mutations previously associated with colistin resistance are clade-associated and present in susceptible isolates, showing no correlation with colistin resistance. In conclusion, the present study provides relevant data on the genetic background of genes involved with colistin resistance deeply rooted across monophyletic groups and provides a better understanding of the genes and mutations involved in colistin resistance.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationInt J Antimicrob Agents . 2022 Jun;59(6):106581pt_PT
dc.identifier.doi10.1016/j.ijantimicag.2022.106581pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.17/4481
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherElsevierpt_PT
dc.subjectAnti-Bacterial Agents / pharmacologypt_PT
dc.subjectAnti-Bacterial Agents / therapeutic usept_PT
dc.subjectBacterial Proteins / geneticspt_PT
dc.subjectColistin* / pharmacologypt_PT
dc.subjectDrug Resistance, Bacterial / geneticspt_PT
dc.subjectKlebsiella Infections* / drug therapypt_PT
dc.subjectKlebsiella pneumoniaept_PT
dc.subjectMicrobial Sensitivity Testspt_PT
dc.subjectMutationpt_PT
dc.subjectPhylogenypt_PT
dc.subjectbeta-Lactamases / geneticspt_PT
dc.subjectHDE PAT CLINpt_PT
dc.titleA Phylogenomic Approach for the Analysis of Colistin Resistance-Associated Genes in Klebsiella Pneumoniae, its Mutational Diversity and Implications for Phenotypic Resistancept_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.issue6pt_PT
oaire.citation.startPage106581pt_PT
oaire.citation.titleInternational Journal of Antimicrobial Agentspt_PT
oaire.citation.volume59pt_PT
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT

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