Colistin Resistance Onset Strategies and Genomic Mosaicism in Clinical <i>Acinetobacter baumannii</i> Lineages

The treatment of multidrug-resistant Gram-negative infections is based on colistin. As result, COL-resistance (COL-R) can develop and spread. In <i>Acinetobacter baumannii</i>, a crucial step is to understand COL-R onset and stability, still far to be elucidated. COL-R phenotypic stabili...

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Autores principales:	Viviana Cafiso, Stefano Stracquadanio, Veronica Dovere, Flavia Lo Verde, Alessandra Zega, Giuseppe Pigola, Simona Barnini, Emilia Ghelardi, Stefania Stefani
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	<i>A. baumannii</i> colistin resistance stability genomic mosaicism phylogenetic lineages Medicine R
Acceso en línea:	https://doaj.org/article/d06219dbf60e413c91b2ddad7cce5adc
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spelling	oai:doaj.org-article:d06219dbf60e413c91b2ddad7cce5adc2021-11-25T18:38:52ZColistin Resistance Onset Strategies and Genomic Mosaicism in Clinical <i>Acinetobacter baumannii</i> Lineages10.3390/pathogens101115162076-0817https://doaj.org/article/d06219dbf60e413c91b2ddad7cce5adc2021-11-01T00:00:00Zhttps://www.mdpi.com/2076-0817/10/11/1516https://doaj.org/toc/2076-0817The treatment of multidrug-resistant Gram-negative infections is based on colistin. As result, COL-resistance (COL-R) can develop and spread. In <i>Acinetobacter baumannii</i>, a crucial step is to understand COL-R onset and stability, still far to be elucidated. COL-R phenotypic stability, onset modalities, and phylogenomics were investigated in a clinical <i>A. baumannii</i> sample showing a COL resistant (COL<sup>R</sup>) phenotype at first isolation. COL-R was confirmed by Minimum-Inhibitory-Concentrations as well as investigated by Resistance-Induction assays and Population-Analysis-Profiles (PAPs) to determine: (i) stability; (ii) inducibility; (iii) heteroresistance. Genomics was performed by Mi-Seq Whole-Genome-Sequencing, Phylogenesis, and Genomic Epidemiology by bioinformatics. COL<sup>R</sup><i>A. baumannii</i> were subdivided as follows: (i) 3 <i>A. baumannii</i> with stable and high COL MICs defining the “homogeneous-resistant” onset phenotype; (ii) 6 <i>A. baumannii</i> with variable and lower COL MICs displaying a “COL-inducible” onset phenotype responsible for adaptive-resistance or a “subpopulation” onset phenotype responsible for COL-heteroresistance. COL-R stability and onset strategies were not uniquely linked to the amount of LPS and cell envelope charge. Phylogenomics categorized 3 lineages clustering stable and/or unstable COL-R phenotypes with increasing genomic complexity. Likewise, different nsSNP profiling in genes already associated with COL-R marked the stable and/or unstable COL-R phenotypes. Our investigation finds out that <i>A. baumannii</i> can range through unstable or stable COL<sup>R</sup> phenotypes emerging via different “onset strategies” within phylogenetic lineages displaying increasing genomic mosaicism.Viviana CafisoStefano StracquadanioVeronica DovereFlavia Lo VerdeAlessandra ZegaGiuseppe PigolaSimona BarniniEmilia GhelardiStefania StefaniMDPI AGarticle<i>A. baumannii</i>colistin resistance stabilitygenomic mosaicismphylogenetic lineagesMedicineRENPathogens, Vol 10, Iss 1516, p 1516 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	<i>A. baumannii</i> colistin resistance stability genomic mosaicism phylogenetic lineages Medicine R
spellingShingle	<i>A. baumannii</i> colistin resistance stability genomic mosaicism phylogenetic lineages Medicine R Viviana Cafiso Stefano Stracquadanio Veronica Dovere Flavia Lo Verde Alessandra Zega Giuseppe Pigola Simona Barnini Emilia Ghelardi Stefania Stefani Colistin Resistance Onset Strategies and Genomic Mosaicism in Clinical <i>Acinetobacter baumannii</i> Lineages
description	The treatment of multidrug-resistant Gram-negative infections is based on colistin. As result, COL-resistance (COL-R) can develop and spread. In <i>Acinetobacter baumannii</i>, a crucial step is to understand COL-R onset and stability, still far to be elucidated. COL-R phenotypic stability, onset modalities, and phylogenomics were investigated in a clinical <i>A. baumannii</i> sample showing a COL resistant (COL<sup>R</sup>) phenotype at first isolation. COL-R was confirmed by Minimum-Inhibitory-Concentrations as well as investigated by Resistance-Induction assays and Population-Analysis-Profiles (PAPs) to determine: (i) stability; (ii) inducibility; (iii) heteroresistance. Genomics was performed by Mi-Seq Whole-Genome-Sequencing, Phylogenesis, and Genomic Epidemiology by bioinformatics. COL<sup>R</sup><i>A. baumannii</i> were subdivided as follows: (i) 3 <i>A. baumannii</i> with stable and high COL MICs defining the “homogeneous-resistant” onset phenotype; (ii) 6 <i>A. baumannii</i> with variable and lower COL MICs displaying a “COL-inducible” onset phenotype responsible for adaptive-resistance or a “subpopulation” onset phenotype responsible for COL-heteroresistance. COL-R stability and onset strategies were not uniquely linked to the amount of LPS and cell envelope charge. Phylogenomics categorized 3 lineages clustering stable and/or unstable COL-R phenotypes with increasing genomic complexity. Likewise, different nsSNP profiling in genes already associated with COL-R marked the stable and/or unstable COL-R phenotypes. Our investigation finds out that <i>A. baumannii</i> can range through unstable or stable COL<sup>R</sup> phenotypes emerging via different “onset strategies” within phylogenetic lineages displaying increasing genomic mosaicism.
format	article
author	Viviana Cafiso Stefano Stracquadanio Veronica Dovere Flavia Lo Verde Alessandra Zega Giuseppe Pigola Simona Barnini Emilia Ghelardi Stefania Stefani
author_facet	Viviana Cafiso Stefano Stracquadanio Veronica Dovere Flavia Lo Verde Alessandra Zega Giuseppe Pigola Simona Barnini Emilia Ghelardi Stefania Stefani
author_sort	Viviana Cafiso
title	Colistin Resistance Onset Strategies and Genomic Mosaicism in Clinical <i>Acinetobacter baumannii</i> Lineages
title_short	Colistin Resistance Onset Strategies and Genomic Mosaicism in Clinical <i>Acinetobacter baumannii</i> Lineages
title_full	Colistin Resistance Onset Strategies and Genomic Mosaicism in Clinical <i>Acinetobacter baumannii</i> Lineages
title_fullStr	Colistin Resistance Onset Strategies and Genomic Mosaicism in Clinical <i>Acinetobacter baumannii</i> Lineages
title_full_unstemmed	Colistin Resistance Onset Strategies and Genomic Mosaicism in Clinical <i>Acinetobacter baumannii</i> Lineages
title_sort	colistin resistance onset strategies and genomic mosaicism in clinical <i>acinetobacter baumannii</i> lineages
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/d06219dbf60e413c91b2ddad7cce5adc
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Colistin Resistance Onset Strategies and Genomic Mosaicism in Clinical <i>Acinetobacter baumannii</i> Lineages

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