A Phylogenomic Approach for the Analysis of Colistin Resistance-Associated Genes in Klebsiella Pneumoniae, its Mutational Diversity and Implications for Phenotypic Resistance
Autor(a) principal: | |
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Data de Publicação: | 2022 |
Outros Autores: | , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10400.17/4481 |
Resumo: | The 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. |
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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 ResistanceAnti-Bacterial Agents / pharmacologyAnti-Bacterial Agents / therapeutic useBacterial Proteins / geneticsColistin* / pharmacologyDrug Resistance, Bacterial / geneticsKlebsiella Infections* / drug therapyKlebsiella pneumoniaeMicrobial Sensitivity TestsMutationPhylogenybeta-Lactamases / geneticsHDE PAT CLINThe 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.ElsevierRepositório do Centro Hospitalar Universitário de Lisboa Central, EPEElias, RSpadar, APhelan, JMelo-Cristino, JLito, LPinto, MGonçalves, LCampino, SClark, TGDuarte, APerdigão, J2023-04-12T14:45:26Z20222022-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.17/4481engInt J Antimicrob Agents . 2022 Jun;59(6):10658110.1016/j.ijantimicag.2022.106581info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-04-16T05:45:32Zoai:repositorio.chlc.min-saude.pt:10400.17/4481Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T17:49:36.187363Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
A Phylogenomic Approach for the Analysis of Colistin Resistance-Associated Genes in Klebsiella Pneumoniae, its Mutational Diversity and Implications for Phenotypic Resistance |
title |
A Phylogenomic Approach for the Analysis of Colistin Resistance-Associated Genes in Klebsiella Pneumoniae, its Mutational Diversity and Implications for Phenotypic Resistance |
spellingShingle |
A Phylogenomic Approach for the Analysis of Colistin Resistance-Associated Genes in Klebsiella Pneumoniae, its Mutational Diversity and Implications for Phenotypic Resistance Elias, R Anti-Bacterial Agents / pharmacology Anti-Bacterial Agents / therapeutic use Bacterial Proteins / genetics Colistin* / pharmacology Drug Resistance, Bacterial / genetics Klebsiella Infections* / drug therapy Klebsiella pneumoniae Microbial Sensitivity Tests Mutation Phylogeny beta-Lactamases / genetics HDE PAT CLIN |
title_short |
A Phylogenomic Approach for the Analysis of Colistin Resistance-Associated Genes in Klebsiella Pneumoniae, its Mutational Diversity and Implications for Phenotypic Resistance |
title_full |
A Phylogenomic Approach for the Analysis of Colistin Resistance-Associated Genes in Klebsiella Pneumoniae, its Mutational Diversity and Implications for Phenotypic Resistance |
title_fullStr |
A Phylogenomic Approach for the Analysis of Colistin Resistance-Associated Genes in Klebsiella Pneumoniae, its Mutational Diversity and Implications for Phenotypic Resistance |
title_full_unstemmed |
A Phylogenomic Approach for the Analysis of Colistin Resistance-Associated Genes in Klebsiella Pneumoniae, its Mutational Diversity and Implications for Phenotypic Resistance |
title_sort |
A Phylogenomic Approach for the Analysis of Colistin Resistance-Associated Genes in Klebsiella Pneumoniae, its Mutational Diversity and Implications for Phenotypic Resistance |
author |
Elias, R |
author_facet |
Elias, R Spadar, A Phelan, J Melo-Cristino, J Lito, L Pinto, M Gonçalves, L Campino, S Clark, TG Duarte, A Perdigão, J |
author_role |
author |
author2 |
Spadar, A Phelan, J Melo-Cristino, J Lito, L Pinto, M Gonçalves, L Campino, S Clark, TG Duarte, A Perdigão, J |
author2_role |
author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Repositório do Centro Hospitalar Universitário de Lisboa Central, EPE |
dc.contributor.author.fl_str_mv |
Elias, R Spadar, A Phelan, J Melo-Cristino, J Lito, L Pinto, M Gonçalves, L Campino, S Clark, TG Duarte, A Perdigão, J |
dc.subject.por.fl_str_mv |
Anti-Bacterial Agents / pharmacology Anti-Bacterial Agents / therapeutic use Bacterial Proteins / genetics Colistin* / pharmacology Drug Resistance, Bacterial / genetics Klebsiella Infections* / drug therapy Klebsiella pneumoniae Microbial Sensitivity Tests Mutation Phylogeny beta-Lactamases / genetics HDE PAT CLIN |
topic |
Anti-Bacterial Agents / pharmacology Anti-Bacterial Agents / therapeutic use Bacterial Proteins / genetics Colistin* / pharmacology Drug Resistance, Bacterial / genetics Klebsiella Infections* / drug therapy Klebsiella pneumoniae Microbial Sensitivity Tests Mutation Phylogeny beta-Lactamases / genetics HDE PAT CLIN |
description |
The 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. |
publishDate |
2022 |
dc.date.none.fl_str_mv |
2022 2022-01-01T00:00:00Z 2023-04-12T14:45:26Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10400.17/4481 |
url |
http://hdl.handle.net/10400.17/4481 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Int J Antimicrob Agents . 2022 Jun;59(6):106581 10.1016/j.ijantimicag.2022.106581 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Elsevier |
publisher.none.fl_str_mv |
Elsevier |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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1799131577196740608 |