Gene dependence during mammalian Acinetobacter baumannii pneumonia and septicaemia infections

With a limited number of traditional virulence factors, the success of the nosocomial pathogen <i>Acinetobacter baumannii</i> 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 <i>in vivo</i> pathogenesis have yet to be fully elucidated. This study utilized the <i>A. baumannii</i> AB5075-UW transposon mutant library with unbiased genome-wide transposon sequencing to identify the genetic basis for survival and fitness during pneumonia and septicaemia infections. We identified 128 genes essential for in-host survival, including 22 required for survival in all tissues. Additionally, 302 genes with significantly altered fitness <i>in vivo</i> were also identified. Tissue specificity was observed, highlighting the importance of genes associated with aa biosynthesis in the lungs, cell shape and structure in the kidneys and metal acquisition during septicaemia. The majority (89%) of the genes with aberrant fitness were constituents of the core <i>A. baumannii</i> genome. The findings were validated using a subset of targeted mutants, including those required for infection (<i>phoB</i>, <i>cysI</i> and <i>hom</i>) or specifically septicaemia (<i>corA</i>, <i>lepA</i> and <i>purN</i>) or pneumonia (<i>argC</i>, <i>hisC</i> and <i>leuD</i>), confirming that these observations were a result of specific <i>in vivo</i> fitness defects rather than aberrant <i>in vitro</i> growth. Taken together, these data provide the first global profile of genes required for <i>in vivo</i> fitness of <i>A. baumannii</i> during different disease states and growth in different tissues.