Targeting key virulence factors in Staphylococcus aureus during the initial phase of infection using omics and live cell microscopy analyses
Staphylococcus aureus (S. aureus) is a major pathogen and causes several types of serious hospital-, community-acquired and livestock-associated diseases. To understand, prevent and fight the infection process in for example bovine mastitis, more knowledge about virulence mechanisms is needed. This project will focus on the role and activity of S. aureus virulence factors during infection and their significance for the ability of S. aureus to invade epithelial cells. An integrated omics- and live cell microscopy based approach of S. aureus strains, isolated from bovine mastitis, will be performed. S. aureus key virulence factors important for pathogenicity will be identified and whole genome sequencing accomplished. Expression and significance of selected virulence factors will be studied in an infection model based on mammary epithelial cells. S. aureus deletion mutants will be generated and compared to the isogenic wild types regarding infection ability. Incorporating of fluorescent reporter proteins into S. aureus will enable enrichment and separation from host cells by flow cytometry. Host-pathogen interaction will be studied with time-lapse microscopy monitoring of bacterial invasion, mRNA expression of bacterial virulence factors investigated by RT-PCR and proteomic methods used to characterize the evolution of the proteome during infection. Unique virulence proteins identified are candidates to become biomarkers and vaccine targets.
|Effective start/end date||2017/01/01 → 2020/12/31|
- Lund University (lead)
- Swedish National Veterinary Institute
- Uppsala University