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: | , , , , , , , , |
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| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
MDPI AG
2021
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| Materias: | |
| Acceso en línea: | https://doaj.org/article/d06219dbf60e413c91b2ddad7cce5adc |
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| Sumario: | 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. |
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