Journal
JOURNAL OF INVESTIGATIVE DERMATOLOGY
Volume 131, Issue 4, Pages 907-915Publisher
ELSEVIER SCIENCE INC
DOI: 10.1038/jid.2010.417
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Funding
- National Institutes of Health [R24 CA92865]
- Dermatologic Research Foundation of California
- [R01 AI078910]
- [R03 AR054534]
- [R01 AI059091]
- [T32 AR058921]
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Staphylococcus aureus skin infections represent a significant public health threat because of the emergence of antibiotic-resistant strains such as methicillin-resistant S. aureus (MRSA). As greater understanding of protective immune responses and more effective antimicrobial therapies are needed, a S. aureus skin wound infection model was developed in which full-thickness scalpel cuts on the backs of mice were infected with a bioluminescent S. aureus (methicillin sensitive) or USA300 community-acquired MRSA strain and in vivo imaging was used to noninvasively monitor the bacterial burden. In addition, the infection-induced inflammatory response was quantified using in vivo fluorescence imaging of LysEGFP mice. Using this model, we found that both IL-1 alpha and IL-1 beta contributed to host defense during a wound infection, whereas IL-1 beta was more critical during an intradermal S. aureus infection. Furthermore, treatment of a USA300 MRSA skin infection with retapamulin ointment resulted in up to 85-fold reduction in bacterial burden and a 53% decrease in infection-induced inflammation. In contrast, mupirocin ointment had minimal clinical activity against this USA300 strain, resulting in only a 2-fold reduction in bacterial burden. Taken together, this S. aureus wound infection model provides a valuable preclinical screening method to investigate cutaneous immune responses and the efficacy of topical antimicrobial therapies. Journal of Investigative Dermatology (2011) 131, 907-915; doi:10.1038/jid.2010.417; published online 30 December 2010
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