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Identification of novel virulence factors of S. aureus

S. aureus is of considerable clinical concern due to its significant morbidity and mortality as well as its resistance to antibiotics. Attempts at developing a suitable vaccine have not been successful to date. This would suggest that although many virulence factors of S. aureus have been identified and well studied, other uncharacterized products important in infection are ill-defined. To identify new virulence factors of S. aureus we have conducted a genome wide Tn-seq screen. This has identified over 100 genes that appear to be important for in vivo fitness in an animal model of acute pneumonia. We are currently characterizing these genes and their role in various in vitro and in vivo assays to better define their roles in pathogenesis. Projects include understanding the role of metabolism in acute and chronic infections, influence in cellular respiration and how energy output can influence tolerance to antimicrobials.

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Figure 1.  S. aureus genes required for pulmonary infection identified by Tn-seq analysis. A) CIRCOS plot of Tn-seq data. The outer ring provides the base count of the S. aureus genome. The red tiles mark genes designated as essential from this study. The following ring with blue tiles depicts genes called essential in prior studies and the green tiles are genes classed as essential across all studies. Five rings (black) depict read counts for each mouse analyzed. Mouse reads are shown as histograms with decreases (yellow-red) and increases (green-blue) shaded underneath based on the magnitude of change. The innermost ring (blue) highlights gene identified as conditionally essential in the pneumonia infection model

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