Colistin Resistance Onset Strategies and Genomic Mosaicism in Clinical Acinetobacter baumannii Lineages

Pathogens

Simona Barnini¹  Viviana Cafiso²  Giuseppe Pigola²  Alessandra Zega²  Stefano Stracquadanio²  Flavia Lo Verde²  Stefania Stefani²  Veronica Dovere³  Emilia Ghelardi³ 

[1] Bacteriology Unit of Azienda Ospedaliero-Universitaria Pisana, 56126 Pisa, Italy;Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy;Department of Translational Research and New Technology in Medicine and Surgery, Azienda Ospedaliero-Universitaria Pisana, University of Pisa, 56126 Pisa, Italy;

关键词: A. baumannii;    colistin resistance stability;    genomic mosaicism;    phylogenetic lineages;   

DOI  :  10.3390/pathogens10111516

来源: DOAJ

【 摘 要 】

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 (COL^R) 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^RA. 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 COL^R phenotypes emerging via different “onset strategies” within phylogenetic lineages displaying increasing genomic mosaicism.

【 授权许可】

Unknown