archives@tulane.edu / The rise in prevalence of antimicrobial resistance is one the greatest public health concerns the world is facing today. As the incidence of antimicrobial resistance climbs, persistent wound and surgical site infections are becoming more common, with multidrug resistant Staphylococcus aureus and Pseudomonas aeruginosa being two of the most frequently identified causative agents. To combat these drug resistant infections, there is an urgent need to develop novel therapeutics. In this work, we developed and validated a splinted full thickness murine wound model used in tandem with bioluminescent strains of bacteria to study bacterial infection, wound healing, and novel therapeutics. Upon the validation of the model, we use it to evaluate the topical antimicrobial efficacy of three novel antimicrobials: bacterial derived outer membrane vesicles (OMVs), the antiseptic ‘ASP’, and the peptide D-CONGA. Though OMVs ultimately exacerbate wound infection and healing, we demonstrate that ‘ASP’ and D-CONGA possess broad spectrum antimicrobial and antibiofilm activity with minimal impact on wound healing. With success in evaluating antimicrobials we next use the wound infection model to evaluate the role of the immune cytokine IL-22 in bacterial clearance and healing in the context of MRSA and P. aeruginosa infections in addition to the potential use of IL-22 as a topical therapeutic. We demonstrate that enhanced IL-22 signaling positively influences both wound healing and gross wound pathology in P. aeruginosa wound infections and that topical treatment of IL-22 promotes wound healing in MRSA infected mice. Further we show that infection with P. aeruginosa enhances the expression of IL-22, while wounding enhances the expression of IL-22 receptor (IL-22R) regardless of infection status. Ultimately the completion of this work demonstrates the utility and reproducibility of the full thickness splinted wound model used in conjunction with bioluminescent bacteria for the study of infection progression, healing, antimicrobial therapeutics, and innate immunity, while also providing insight into IL-22’s role in skin infections. / 1 / Hoffmann, Joseph
| Identifer | oai:union.ndltd.org:TULANE/oai:http://digitallibrary.tulane.edu/:tulane_121696 |
| Date | January 2020 |
| Contributors | Hoffmann, Joseph (author), Morici, Lisa (Thesis advisor), School of Medicine Biomedical Sciences Graduate Program (Degree granting institution) |
| Publisher | Tulane University |
| Source Sets | Tulane University |
| Language | English |
| Detected Language | English |
| Type | Text |
| Format | electronic, pages: 186 |
| Rights | No embargo, Copyright is in accordance with U.S. Copyright law. |
Page generated in 0.0025 seconds