Study of virulence factors associated with Acinetobacter baumannii systemic and gastrointestinal infections

Multi-drug resistant Acinetobacter baumannii is among the most prevalent bacterial pathogens associated with trauma-related wound and bloodstream infections. Gastrointestinal (GI) tract colonization may contribute to emergence of these MDR A. baumannii isolates. Furthermore, while neutrophils are known to be essential for A. baumannii clearance, little else is known about either the protective host immune response to this pathogen, or virulence factors associated with it. In these studies, we set out to determine the host response to virulence factors associated with A. baumannii with the following specific aims: 1) elucidate the role of pentraxin 3 (PTX3) found in neutrophilic granules in A. baumannii sepsis, 2) elucidate the role of SIgA in A. baumannii GI tract colonization, and 3) characterize the interaction between A. baumannii and SIgA. First, utilizing an intraperitoneal sepsis challenge model, we observed that elevated PTX3 production following A. baumannii challenge was associated with increased morbidity and mortality. Next, we observed enhancement of A. baumannii GI tract colonization in the presence of SIgA using an oral GI challenge model. Finally, using RNAseq and in vitro culture, we found that thioredoxin may contribute to GI tract colonization. These studies ultimately lead us to generate a thioredoxin deletion mutant and corresponding complemented strain for use in future studies to further elucidate the role of thioredoxin in A. bauamannii GI tract colonization.