Identifying niche specific adaptations in Acinetobacter baumannii. Acinetobacter baumannii

Acinetobacter baumannii (Ab), the most clinically relevant member of the Acinetobacter genus, is an opportunistic pathogen. This bacterium has an alarming predisposition to acquire multi-drug resistance (MDR), and infections associated with MDR-Ab strains are linked to greater morbidity and mortality. Accordingly, carbapenem-resistant Ab recently topped the WHO priority list of bacteria that require research and development of novel therapeutic strategies. Despite the significant worldwide impact of MDR-Ab, when compared to other major MDR pathogens, relatively little is known about Ab pathogenesis. Although Ab most commonly causes pneumonia (40 % of cases), Ab also commonly infects other niches such as blood, the urinary tract, and soft-tissues. Classically, Ab strains are regarded as a homogenous group of opportunistic pathogens displaying niche-indiscriminate virulence in critically-ill hosts. As a result, Ab research efforts often extrapolate findings from one Ab strain in a single model of infection to draw conclusions about Ab as a whole. Recent data from has challenged the concept that Ab lacks niche-specificity. Employing a catheter-associated urinary tract infection model, we have collected evidence that there are genetic determinants in Ab that influence both niche specificity and the infection outcome. We have infected mice with Ab strains from urinary and respiratory sources and identified strains that perform well in one infection model, but poorly in the other. We hypothesize that genetically determined, niche-specific adaptations have occurred in modern Ab strains. Employing comparative genomics we will determine the genetic elements responsible for niche-specific adaptations. We expect to identify niche-specific virulence determinants that may be novel targets for innovative antibiotic-independent therapies.