# Phenotypic and genetic heterogeneity of Acinetobacter baumannii in the course of an animal chronic infection

## TL;DR

This study examines how Acinetobacter baumannii evolves genetically and phenotypically during a 5-year urinary tract infection in an animal patient after antibiotic treatment was stopped.

## Contribution

The study reveals genetic and phenotypic adaptations of A. baumannii during a chronic infection without antibiotic pressure.

## Key findings

- A. baumannii strains showed genome reduction through IS recombination, phage excision, and plasmid curing.
- Genetic variations were observed in biofilm formation and adhesion genes, but metabolism remained stable.
- Colistin resistance was preserved due to a pmrB mutation despite overall decreased antibiotic resistance.

## Abstract

Acinetobacter baumannii is a nosocomial pathogen associated with various infections, including urinary tract infections (UTIs). In the course of an infection, A. baumannii is known to rapidly become resistant to antibiotic therapy, but much less is known about possible adaptation without antibiotic pressure. Through a retrospective study, we investigated within-host genetic diversity during a subclinical 5-year UTI in an animal–patient after withdrawal of colistin treatment. We conducted whole-genome sequencing and phenotypic assays on 17 clonally related isolates from the Sequence Type 25 lineage. Phylogenomic analysis revealed their proximity with animal and human strains from the same country suggesting zoonotic transmission (France). In this case study, the clonally related strains presented variations in genome sizes and nucleotide sequences. Over the course of the infection, A. baumannii underwent genome reduction through insertion sequence (IS) recombination, phage excision or plasmid curing. Alongside this global genome reduction, we observed an expansion of IS17, initially located on the endogenous large plasmid. Genetic variations were mainly located in biofilm formation and metabolism genes. We observed repeated variations affecting three biofilm genes and two adhesion operons associated with weak biofilm-forming capacity. Conversely, only two metabolic genes were recurrently affected, and phenotypic assays indicated a rather stable metabolism profile between the isolates suggesting minor adaptations to its host. Lastly, an overall decreased antibiotic resistance – expected in the absence of antibiotic treatment – contrasted with a conserved colistin resistance due to a pmrB mutation among the isolates.