Reduced Fitness Costs of <italic toggle="yes">mcr-1.2</italic> Compared to Mutated <italic toggle="yes">pmrB</italic> in Isogenic Colistin-Resistant KPC-3-Producing <named-content content-type="genus-species">Klebsiella pneumoniae</named-content>

ABSTRACT In the present study, we provide the results of a detailed genomic analysis and the growth characteristics of a colistin-resistant KPC-3-producing Klebsiella pneumoniae sequence type 512 (ST512) isolate (the colR-KPC3-KP isolate) with a mutated pmrB and isogenic isolates of colR-KPC3-KP wit...

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Autores principales:	Cesira Giordano, Adrian Klak, Simona Barnini, Monika A. Chlebowicz, Mariacristina Menconi, John W. Rossen, Alexander W. Friedrich, Erik Bathoorn
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	colistin fitness cost mcr-1.2 molecular epidemiology Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/4b7162f14b10463f9b0c1b72fb88e820
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spelling	oai:doaj.org-article:4b7162f14b10463f9b0c1b72fb88e8202021-11-15T15:22:24ZReduced Fitness Costs of <italic toggle="yes">mcr-1.2</italic> Compared to Mutated <italic toggle="yes">pmrB</italic> in Isogenic Colistin-Resistant KPC-3-Producing <named-content content-type="genus-species">Klebsiella pneumoniae</named-content>10.1128/mSphere.00551-192379-5042https://doaj.org/article/4b7162f14b10463f9b0c1b72fb88e8202019-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00551-19https://doaj.org/toc/2379-5042ABSTRACT In the present study, we provide the results of a detailed genomic analysis and the growth characteristics of a colistin-resistant KPC-3-producing Klebsiella pneumoniae sequence type 512 (ST512) isolate (the colR-KPC3-KP isolate) with a mutated pmrB and isogenic isolates of colR-KPC3-KP with mcr-1.2 isolated from an immunocompromised patient. From 2014 to 2017, four colR-KPC3-KP isolates were detected in rectal swab samples collected from a pediatric hematology patient at the Azienda Ospedaliero-Universitaria Pisana in Pisa, Italy. Whole-genome sequencing was performed by MiSeq sequencing (Illumina). Growth experiments were performed using different concentrations of colistin. The growth lag phases both of an isolate harboring a deletion in pmrB and of clonal variants with mcr-1.2 were assessed by the use of real-time light-scattering measurements. In the first isolate (isolate 1000-pmrBΔ, recovered in September 2014), a 17-nucleotide deletion in pmrB was detected. In subsequent isolates, the mcr-1.2 gene associated with the plasmid pIncX4-AOUP was found, while pmrB was intact. Additionally, plasmid pIncQ-AOUP, harboring aminoglycoside resistance genes, was detected. The growth curves of the first three isolates were identical without colistin exposure; however, at higher concentrations of colistin, the growth curves of the isolate with a deletion in pmrB showed longer lag phases. We observed the replacement of mutated colR-KPC3-KP pmrB by isogenic isolates with multiple resistance plasmids, including mcr-1.2-carrying pIncX4, probably due to coselection under gentamicin treatment in a patient with prolonged colR-KPC3-KP carriage. The carriage of these isolates persisted in follow-up cultures. Coselection and the advantages in growth characteristics suggest that the plasmid-mediated resistance conferred by mcr has fewer fitness costs in colR-KPC3-KP than mutations in chromosomal pmrB, contributing to the success of this highly resistant hospital-adapted epidemiological lineage. IMPORTANCE Our study shows a successful prolonged human colonization by a colistin-resistant Klebsiella pneumoniae isolate harboring mcr-1.2. An intense antibiotic therapy contributed to the maintenance of this microorganism through the acquisition of new resistance genes. The isolates carrying mcr-1.2 showed fewer fitness costs than isogenic isolates with a pmrB mutation in the chromosome. Coselection and reduced fitness costs may explain the replacement of isolates with the pmrB mutation by other isolates and the ability of the microorganism to persist despite antibiotic treatment.Cesira GiordanoAdrian KlakSimona BarniniMonika A. ChlebowiczMariacristina MenconiJohn W. RossenAlexander W. FriedrichErik BathoornAmerican Society for Microbiologyarticlecolistinfitness costmcr-1.2molecular epidemiologyMicrobiologyQR1-502ENmSphere, Vol 4, Iss 6 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	colistin fitness cost mcr-1.2 molecular epidemiology Microbiology QR1-502
spellingShingle	colistin fitness cost mcr-1.2 molecular epidemiology Microbiology QR1-502 Cesira Giordano Adrian Klak Simona Barnini Monika A. Chlebowicz Mariacristina Menconi John W. Rossen Alexander W. Friedrich Erik Bathoorn Reduced Fitness Costs of <italic toggle="yes">mcr-1.2</italic> Compared to Mutated <italic toggle="yes">pmrB</italic> in Isogenic Colistin-Resistant KPC-3-Producing <named-content content-type="genus-species">Klebsiella pneumoniae</named-content>
description	ABSTRACT In the present study, we provide the results of a detailed genomic analysis and the growth characteristics of a colistin-resistant KPC-3-producing Klebsiella pneumoniae sequence type 512 (ST512) isolate (the colR-KPC3-KP isolate) with a mutated pmrB and isogenic isolates of colR-KPC3-KP with mcr-1.2 isolated from an immunocompromised patient. From 2014 to 2017, four colR-KPC3-KP isolates were detected in rectal swab samples collected from a pediatric hematology patient at the Azienda Ospedaliero-Universitaria Pisana in Pisa, Italy. Whole-genome sequencing was performed by MiSeq sequencing (Illumina). Growth experiments were performed using different concentrations of colistin. The growth lag phases both of an isolate harboring a deletion in pmrB and of clonal variants with mcr-1.2 were assessed by the use of real-time light-scattering measurements. In the first isolate (isolate 1000-pmrBΔ, recovered in September 2014), a 17-nucleotide deletion in pmrB was detected. In subsequent isolates, the mcr-1.2 gene associated with the plasmid pIncX4-AOUP was found, while pmrB was intact. Additionally, plasmid pIncQ-AOUP, harboring aminoglycoside resistance genes, was detected. The growth curves of the first three isolates were identical without colistin exposure; however, at higher concentrations of colistin, the growth curves of the isolate with a deletion in pmrB showed longer lag phases. We observed the replacement of mutated colR-KPC3-KP pmrB by isogenic isolates with multiple resistance plasmids, including mcr-1.2-carrying pIncX4, probably due to coselection under gentamicin treatment in a patient with prolonged colR-KPC3-KP carriage. The carriage of these isolates persisted in follow-up cultures. Coselection and the advantages in growth characteristics suggest that the plasmid-mediated resistance conferred by mcr has fewer fitness costs in colR-KPC3-KP than mutations in chromosomal pmrB, contributing to the success of this highly resistant hospital-adapted epidemiological lineage. IMPORTANCE Our study shows a successful prolonged human colonization by a colistin-resistant Klebsiella pneumoniae isolate harboring mcr-1.2. An intense antibiotic therapy contributed to the maintenance of this microorganism through the acquisition of new resistance genes. The isolates carrying mcr-1.2 showed fewer fitness costs than isogenic isolates with a pmrB mutation in the chromosome. Coselection and reduced fitness costs may explain the replacement of isolates with the pmrB mutation by other isolates and the ability of the microorganism to persist despite antibiotic treatment.
format	article
author	Cesira Giordano Adrian Klak Simona Barnini Monika A. Chlebowicz Mariacristina Menconi John W. Rossen Alexander W. Friedrich Erik Bathoorn
author_facet	Cesira Giordano Adrian Klak Simona Barnini Monika A. Chlebowicz Mariacristina Menconi John W. Rossen Alexander W. Friedrich Erik Bathoorn
author_sort	Cesira Giordano
title	Reduced Fitness Costs of <italic toggle="yes">mcr-1.2</italic> Compared to Mutated <italic toggle="yes">pmrB</italic> in Isogenic Colistin-Resistant KPC-3-Producing <named-content content-type="genus-species">Klebsiella pneumoniae</named-content>
title_short	Reduced Fitness Costs of <italic toggle="yes">mcr-1.2</italic> Compared to Mutated <italic toggle="yes">pmrB</italic> in Isogenic Colistin-Resistant KPC-3-Producing <named-content content-type="genus-species">Klebsiella pneumoniae</named-content>
title_full	Reduced Fitness Costs of <italic toggle="yes">mcr-1.2</italic> Compared to Mutated <italic toggle="yes">pmrB</italic> in Isogenic Colistin-Resistant KPC-3-Producing <named-content content-type="genus-species">Klebsiella pneumoniae</named-content>
title_fullStr	Reduced Fitness Costs of <italic toggle="yes">mcr-1.2</italic> Compared to Mutated <italic toggle="yes">pmrB</italic> in Isogenic Colistin-Resistant KPC-3-Producing <named-content content-type="genus-species">Klebsiella pneumoniae</named-content>
title_full_unstemmed	Reduced Fitness Costs of <italic toggle="yes">mcr-1.2</italic> Compared to Mutated <italic toggle="yes">pmrB</italic> in Isogenic Colistin-Resistant KPC-3-Producing <named-content content-type="genus-species">Klebsiella pneumoniae</named-content>
title_sort	reduced fitness costs of <italic toggle="yes">mcr-1.2</italic> compared to mutated <italic toggle="yes">pmrb</italic> in isogenic colistin-resistant kpc-3-producing <named-content content-type="genus-species">klebsiella pneumoniae</named-content>
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/4b7162f14b10463f9b0c1b72fb88e820
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Reduced Fitness Costs of <italic toggle="yes">mcr-1.2</italic> Compared to Mutated <italic toggle="yes">pmrB</italic> in Isogenic Colistin-Resistant KPC-3-Producing <named-content content-type="genus-species">Klebsiella pneumoniae</named-content>

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