The Role of Bacterial Thioredoxin in Acinetobacter baumannii Virulence and Maintenance of Cell-surface Properties

Multi-drug resistant Acinetobacter baumannii has become one of the most prominent nosocomial infections around the globe. Various predispositions for infection have been noted but the most prevalent is being a patient in an intensive care unit (ICU). Infections are characterized by a large influx of neutrophils, which are required for the host to clear and survive infection. Previous studies in our lab have indicated that the redox protein thioredoxin plays a major role in A. baumannii infections. Thioredoxin, and the thioredoxin system, have previously been explored as novel antimicrobial targets. Multiple drugs already approved or tested by the Federal Drug Administration (FDA) have been found to target the thioredoxin system and could be repurposed for this use. In these studies, we aimed to characterize the role of thioredoxin in A. baumannii virulence using a thioredoxin-null strain. First, we analyzed the physical characteristics of the mutant and then looked at genomic differences between the mutant and the WT. Next, we explored the role of thioredoxin in maintaining cell surface hydrophobicity and noted that changes in cell surface hydrophobicity were also seen in a second Gram-negative organism. Finally, we explored the role of secondary infection during A. baumannii challenge and utilized a thioredoxin inhibitor to explore the possibility of targeting the thioredoxin system of A. baumannii for anti-bacterial effects. These data indicate that thioredoxin is a virulence factor in A. baumannii pulmonary infections and that targeting the thioredoxin system in this bacterium could be a viable anti-bacterial option.