Evolution of Acinetobacter baumannii in Clinical Bacteremia Patients

Introduction: Colonization of the respiratory tract by Acinetobacter baumannii has been established as an independent risk factor for bacteremia. However, within-host evolution of A. baumannii in bacteremia has not been extensively investigated. Methods: We performed whole-genome sequencing to discover the evolutionary characteristics that accompany the transition from respiratory tract carriage to bloodstream infection in three patients with A. baumannii bacteremia. Results: Within-host genetic diversity was identified. A total of 21 single nucleotide variants (SNVs) were detected. Genic and intergenic evolution occurred particularly in secretion system, DNA recombination, and cell motility genes. Intergenic SNVs occurred more frequently compared to synonymous and non-synonymous SNVs, which indicated potential transcription or translation regulation. Non-synonymous mutations mostly occurred during the transition from respiratory tract carriage to bloodstream infection. Isolates of clonal complex 208 (CC208) had lower substitution rate with approximately 10(-6) nucleotide substitutions per site year(-1), compared with non-CC208 isolates (approximately 10(-5)). We found evidence for the occurrence of recombination in one patient. A total of 259 genes were found to be gained or lost during the within-host evolution, and 231 genes were only detected in one patient. Gene function annotation results suggested that most genes (71/259) were related to replication, recombination, and repair. Universal bloodstream specific genes were not found in all three patients, and only one putative membrane protein related gene was lost in two patients. Conclusion: Our results indicated that within-host evolution of A. baumannii bacteremia was driven by mutations, gene content changes, and limited effect of recombination. Gene content diversity between different patients was identified, which suggested interplay of both host and pathogen factors in within-host genetic diversity. Secretion system-related genes showed higher frequency of genomic variations during the within-host evolution. Our findings enhanced our understanding of within-host evolution of A. baumannii bacteremia and provided a framework for discovering novel genomic changes and pathogenicity genes important for bacteremia, which will be validated in future studies.