Acinetobacter baumannii in vivo Tn-seq

With a limited number of traditional virulence factors, the success of the nosocomial pathogen Acinetobacter baumannii is largely attributed to its ability to persist and resist. The niches encountered during infection vary significantly from the more commonly studied laboratory setting, and consequently, the genes responsible for in vivo pathogenesis have yet to be fully elucidated. This study utilized the A. baumannii AB5075-UW transposon mutant library with unbiased genome-wide transposon sequencing to identify the genetic basis for survival and fitness during pneumonia and septicemia infections. We identified 128 genes essential for survival, including 22 required for survival in all tissues. Additionally, 302 genes with significantly altered fitness in vivo were also identified. Tissue-specificity was observed, highlighting the importance of genes associated with amino acid biosynthesis in the lungs, cell shape and structure in the kidneys, and metal acquisition during septicemia. The majority (89%) of the genes with aberrant fitness were constituents of the core A. baumannii genome. The findings were validated using a subset of targeted mutants, confirming these observations were a result of specific in vivo fitness defects rather than aberrant in vitro growth. Taken together, these data provide the first global profile of genes required for in vivo fitness of A. baumannii during different disease states and growth in different tissues.