Dual gene expression analysis identifies factors associated with Staphylococcus aureus virulence in diabetic mice

Rudy Jacquet, Annette E. LaBauve, Lavoisier Akoolo, Shivani Patel, Abdulelah A. Alqarzaee, Tania Wong Fok Lung, Kunal Poorey, Timothy P. Stinear, Vinai C. Thomas, Robert Meagher, Dane Parker
2019 Infection and Immunity  
Staphylococcus aureus is a major human pathogen of the skin. The global burden of diabetes is high, with S. aureus a major complication of diabetic wound infections. We investigated how the diabetic environment influences S. aureus skin infection and observed an increased susceptibility to infection in mouse models of both type I and type II diabetes. A dual gene expression approach was taken to investigate transcriptional alterations in both the host and bacterium after infection. While
more » ... s of the host response revealed only minor changes between infected control and diabetic mice, we observed that S. aureus isolated from diabetic mice had significant increases in genes associated with translation, posttranslational modification and chaperones, and reductions in genes associated with amino acid transport and metabolism. One family of genes upregulated in S. aureus isolated from diabetic lesions encoded the Clp proteases associated with the misfolded protein response. The Clp proteases were found to be partially glucose regulated as well as influencing the hemolytic activity of S. aureus. Strains lacking the Clp proteases, ClpX, ClpC and ClpP were significantly attenuated in our animal model of skin infection, with significant reductions observed in dermonecrosis and bacterial burden. In particular, mutations in clpP and clpX were significantly attenuated and remained attenuation in both normal and diabetic mice. Our data suggests that the diabetic environment also causes changes to occur in invading pathogens and one of these virulence determinants is the Clp protease system.
doi:10.1128/iai.00163-19 pmid:30833333 pmcid:PMC6479027 fatcat:bjpyha23brdolldrwecnpi22li