title: Noninvasive in vivo imaging to evaluate immune responses and antimicrobial therapy against Staphylococcus aureus and USA300 MRSA skin infections.
abstract: 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-1α and IL-1β contributed to host defense during a wound infection, whereas IL-1β 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.
authors.affiliation: Division of Dermatology, David Geffen School of Medicine at UCLA, Los Angeles, California 90095, USA.
authors.forename: John S
authors.initials: JS
authors.lastname: Cho
authors.forename: Jamie
authors.initials: J
authors.lastname: Zussman
authors.forename: Niles P
authors.initials: NP
authors.lastname: Donegan
authors.forename: Romela Irene
authors.initials: RI
authors.lastname: Ramos
authors.forename: Nairy C
authors.initials: NC
authors.lastname: Garcia
authors.forename: Daniel Z
authors.initials: DZ
authors.lastname: Uslan
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Iwakura
authors.forename: Scott I
authors.initials: SI
authors.lastname: Simon
authors.forename: Ambrose L
authors.initials: AL
authors.lastname: Cheung
authors.forename: Robert L
authors.initials: RL
authors.lastname: Modlin
authors.forename: Jenny
authors.initials: J
authors.lastname: Kim
authors.forename: Lloyd S
authors.initials: LS
authors.lastname: Miller
mesh_terms: D000287:Administration, Topical; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D017714:Community-Acquired Infections / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D003872:Dermatitis / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D046169:Dermoscopy / Q000379:methods*; D004195:Disease Models, Animal; D004224:Diterpenes; D016903:Drug Monitoring / Q000379:methods; D049452:Green Fluorescent Proteins / Q000235:genetics; D053582:Interleukin-1alpha / Q000276:immunology; D053583:Interleukin-1beta / Q000276:immunology; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence / Q000379:methods*; D016712:Mupirocin / Q000494:pharmacology*; D013207:Staphylococcal Skin Infections / Q000188:drug therapy / Q000276:immunology / Q000473:pathology
chemical_list: D000900:Anti-Bacterial Agents; D019086:Bridged Bicyclo Compounds, Heterocyclic; D004224:Diterpenes; D053582:Interleukin-1alpha; D053583:Interleukin-1beta; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; C508887:retapamulin; D016712:Mupirocin