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

Abstract

Acinetobacter baumanniiis a nosocomial pathogen associated with various infections, including urinary tract infections (UTIs).A. baumanniiis known to rapidly become resistant to antibiotic therapy, but much less is known about possible adaptation without antibiotic pressure and thereby host-driven evolution. Through a retrospective study, we investigated within-host microevolution during a subclinical five-year UTI in an animal-patient after withdrawal of colistin treatment. We conducted whole-genome sequencing and phenotypic assays on seventeen ST25 isolates. Eight of which were isolated longitudinally throughout the infection timeline while nine others were obtained subsequently to investigate bacterial diversity. We determined that the infection was monophyletic with variations in genome sizes and nucleotide sequences. Over the course of the infection,A. baumanniiunderwent genome reduction through insertion sequence (IS) recombination, phage excision, or plasmid curing. Despite this global genome reduction, we observed an expansion of IS17, initially located on an endogenous plasmid. Gene loss resulted in decreased antibiotic resistance, yet colistin resistance due to apmrBmutation remained stable. All other genetic variations were mainly located in metabolism and biofilm formation genes. Metabolic assays revealed a shift towards as slight decreased metabolic flexibility, presumably adapted to host's urine composition. Moreover, repeated variation affecting biofilm and adhesion genes associated with weak biofilm-forming capacity suggests a genetic drift of repressed genes. This study provides a unique insight into host adaptation of this opportunistic pathogen.