Staphylococcus aureus gene expression during infection and antibiotic treatment with moxifloxacin in a guinea pig biofilm infection model

Staphylococcus aureus is a major agent in device related infections. Upon infection, it upregulates virulence factors and adapts to host environment. We investigated the gene expression profile of S. aureus in a guinea pig infection model. Four Teflon® cages were placed subcutaneously in each of 12 animals prior to inoculation of a S. aureus strain from a patient with prosthetic joint infection (PJI). The animals were divided into two groups of six, one treated with moxifloxacin after three days of infection and for four days, and the other untreated. Cage fluid and cages were collected for RNA sequencing analysis and metabolomics. The gene expression profiles in untreated controls on day 7 and 9 were not differentiable and resemble the profile reported for the PJI case from where the strain originated. Compared to the profiles from day 3, we found upregulation of ammonia production through urea degradation, arginine deiminase and acetoin biosynthesis pathways on day 7 and 9, while several virulence genes were downregulated. Interestingly, the transcriptome seven day after termination of moxifloxacin treatment resembled infection day 3. Overall, the gene expression profiles showed adaptation to hypoxic and acidic environment during infection development. We deem the model to be suitable for pathogenesis studies. Staphylococcus aureus differential gene expression during infection development in a guinea pig infection model. Twelve animals were divided into two groups of six, one treated with moxifloxacin after three days of infection and for four days, and the other untreated. Cage fluid and cages were collected on infection day 3, 7, 9 and 14 for RNA sequencing analysis and metabolomics.