Zhang, Kunyan JrZhang, Jianbo Jr2017-05-012017-05-0120172017Zhang, J. J. (2017). Virulence of a Predominant Community-Associated Methicillin-resistant Staphylococcus aureus Strain USA300 in a Murine Skin Infection Model (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/28642http://hdl.handle.net/11023/3795USA300 is a predominant and highly virulent community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) strain that is a leading cause of skin and soft tissue infections. Herein a murine skin infection model was established to differentiate USA300 virulence from other MRSA strains, and reveal mechanisms contributing to USA300 hypervirulence. In this model, USA300 uniformly presented as dermonecrosis while control strains caused localized skin infection (non-dermonecrosis), which mimicked the key clinical characteristics. It was also observed that the dermonecrosis induced by USA300 was associated with significantly increased neutrophil recruitment and increased production of cytokines/chemokines associated with disease severity. The α-hemolysin (Hla) depletion not only reduced USA300 wildtype virulence in causing skin lesions, but also demonstrated significant effects on reducing neutrophil recruitment and altering local cytokines/chemokines profile. These results suggest that USA300 Hla may induce host response to cause severe skin lesions. This observation may open new opportunities for therapeutic interventions.engUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.Microbiologycommunity-associated methicillin-resistant Staphylococcus aureus (CA-MRSA)USA300dermonecrosismouse skin infection modelα-hemolysin (Hla)master thesis10.11575/PRISM/28642