Phenotype evaluation rawdata of Acinetobacter baumannii harboring chromosomal parallel mutations or an evolved plasmid
Zhang, Linyue (2022), Phenotype evaluation rawdata of Acinetobacter baumannii harboring chromosomal parallel mutations or an evolved plasmid, Dryad, Dataset, https://doi.org/10.5061/dryad.05qfttf4k
OXA-23 is the predominant carbapenemase in carbapenem-resistant Acinetobacter baumannnii. The co-evolutionary dynamics of A. baumannii and OXA-23-encoding plasmids are poorly understood. Here, we transformed A. baumannnii ATCC 17978 with pAZJ221, a blaOXA-23-containing plasmid from a clinical A. baumannnii isolate A221, and subjected the transformant to experimental evolution in the presence of a sub-inhibitory concentration of imipenem for nearly 400 generations. We used population sequencing to track genetic changes at six time-points and evaluated phenotypic changes. Increased fitness of evolving populations, temporary duplication of blaOXA-23 in pAZJ221, interfering allele dynamics, and chromosomal locus-level parallelism were observed. To characterize genotype-to-phenotype associations, we focused on six mutations in parallel targets predicted to affect small RNAs and a cyclic dimeric (3’→5’) GMP-metabolizing protein. Six isogenic mutants with or without pAZJ221 were engineered to test for the causal effects of these mutations on fitness costs and plasmid kinetics, the evolved plasmid containing two copies of blaOXA-23 was transferred to ancestral ATCC 17978. Five of the six mutations contributed to improved fitness in the presence of pAZJ221 under imipenem pressure, and all but one of them impaired plasmid conjugation ability. The duplication of blaOXA-23 contributed to host fitness under carbapenem pressure but imposed a burden on the host in antibiotic-free media relative to the unevolved pAZJ221. Overall, our study provides a framework for the co-evolution of A. baumannii and a clinical blaOXA-23-containing plasmid, involving early blaOXA-23 duplication followed by chromosomal adaptations.