Colistin Resistance Onset Strategies and Genomic Mosaicism in Clinical Acinetobacter baumannii Lineages.
The treatment of multidrug-resistant Gram-negative infections is based on colistin. As result, COL-resistance (COL-R) can develop and spread. In Acinetobacter baumannii, 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 A. baumannii sample showing a COL resistant (COLR) 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. COLRA. baumannii were subdivided as follows: (i) 3 A. baumannii with stable and high COL MICs defining the "homogeneous-resistant" onset phenotype; (ii) 6 A. baumannii 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 A. baumannii can range through unstable or stable COLR phenotypes emerging via different "onset strategies" within phylogenetic lineages displaying increasing genomic mosaicism.
['Cafiso|Viviana|V|0000-0002-0785-7934', 'Stracquadanio|Stefano|S|0000-0003-0653-9560', 'Dovere|Veronica|V|', 'Lo Verde|Flavia|F|', 'Zega|Alessandra|A|', 'Pigola|Giuseppe|G|', 'Barnini|Simona|S|', 'Ghelardi|Emilia|E|0000-0001-6863-1384', 'Stefani|Stefania|S|0000-0003-1594-7427']
genomic mosaicism A. baumannii phylogenetic lineages colistin resistance stability