Evolution of Acinetobacter baumannii in Clinical Bacteremia Patients

Abstract

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.

Host shapes microevolution of MDR Acinetobacter baumannii during long-term infection

“…Our study also present divergences with previous studies on human infections. Indeed, we observed only few mutations in translational machinery genes or in genes related to replication, recombination, and repair (16, 46). However, these evolutions may have been shaped by alternative antibiotic treatments performed on human patients.…”

“…Consequently, there remains a limited understanding of the fate of antibiotic resistance genes and more broadly of gene evolution post-antibiotic exposure and during host colonization. Seminal within-host microevolution studies on A. baumannii observed the accumulation of variations in genes involved surface structures such as motility, adhesion, biofilm formation or cell wall and capsule biogenesis, suggesting a consistent selective pressure during antibiotic-treated infections but phenotypic validation are usually missing (14–16). Phenotypically, antibiotic exposure prompts bacteria to adopt a biofilm-like lifestyle, enhancing their resistance (17).…”

The whole-genome molecular epidemiology of sequential isolates of Acinetobacter baumannii colonizing the rectum of patients in an adult intensive care unit of a tertiary hospital

“…Some studies have indicated that genome changes occur in A. baumannii isolates during antibiotic treatment ( 26 , 27 ), during outbreaks ( 28 ), during studies in a hospital setting over a period of days ( 29 , 30 ), or on sampling of sites other than the digestive tract of a limited number of patients ( 31 – 33 ). It was found that genome changes due to mutation, recombination, and content can occur in a short period of days.…”

The Threat of Carbapenem-Resistant Gram-Negative Bacteria in Patients with Hematological Malignancies: Unignorable Respiratory Non-Fermentative Bacteria-Derived Bloodstream Infections

“… 43 Also, it has been confirmed that the genome of bloodstream isolates was highly homologous to that of respiratory isolates, suggesting that A. baumannii BSI may originate from the respiratory tract. 44 At present, specimens for non-fermentative bacterial screening mainly include sputum, pharyngeal swabs, alveolar lavage fluid. Under the premise of ensuring the positive rate of bacterial screening, non-invasive methods were priority for specimen collection.…”