A Murine Skin Infection Model Capable of Differentiating the Dermatopathology of Community-Associated MRSA Strain USA300 from Other MRSA Strains
Open Access
- 30 January 2021
- journal article
- research article
- Published by MDPI AG in Microorganisms
- Vol. 9 (2), 287
- https://doi.org/10.3390/microorganisms9020287
Abstract
USA300 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. We established a murine intradermal infection model capable of demonstrating dermatopathological differences between USA300 and other MRSA strains. In this model, USA300 induced dermonecrosis, uniformly presenting as extensive open lesions with a histologically documented profound inflammatory cell infiltrate extending below the subcutis. In contrast, USA400 and a colonizing control strain M92 caused only localized non-ulcerated skin infections associated with a mild focal inflammatory infiltrate. It was also determined that the dermonecrosis induced by USA300 was associated with significantly increased neutrophil recruitment, inhibition of an antibacterial response, and increased production of cytokines/chemokines associated with disease severity. These results suggest that induction of severe skin lesions by USA300 is related to over-activation of neutrophils, inhibition of host antibacterial responses, and selective alteration of host cytokine/chemokine profiles.Keywords
Funding Information
- Alberta Innovates (Alberta Sepsis Network)
- Alberta Health Services (Centre for Antimicrobial Resistance (CAR) operation fund)
This publication has 58 references indexed in Scilit:
- Staphylococcal Superantigen-Like Protein 3 Binds to the Toll-Like Receptor 2 Extracellular Domain and Inhibits Cytokine Production Induced by Staphylococcus aureus, Cell Wall Component, or Lipopeptides in Murine MacrophagesInfection and Immunity, 2012
- Neutrophils in innate host defense against Staphylococcus aureus infectionsSeminars in Immunopathology, 2011
- USA300 methicillin-resistant Staphylococcus aureus bacteremia and the risk of severe sepsis: is USA300 methicillin-resistant Staphylococcus aureus associated with more severe infections?Diagnostic Microbiology and Infectious Disease, 2011
- Enhancement of Neutrophil Function by Interleukin-18 Therapy Protects Burn-Injured Mice from Methicillin-Resistant Staphylococcus aureusInfection and Immunity, 2011
- Association of methicillin-resistant Staphylococcus aureus (MRSA) USA300 genotype with mortality in MRSA BacteremiaJournal of Infection, 2010
- Pathogenic Role of Macrophages in Intradermal Infection of Methicillin-Resistant Staphylococcus aureus in Thermally Injured MiceInfection and Immunity, 2010
- Importance of housekeeping gene selection for accurate reverse transcription-quantitative polymerase chain reaction in a wound healing modelWound Repair and Regeneration, 2010
- NOD2 contributes to cutaneous defense againstStaphylococcus aureusthrough α-toxin-dependent innate immune activationProceedings of the National Academy of Sciences of the United States of America, 2009
- Monocyte Chemoattractant Protein-1 (MCP-1): An OverviewJournal of Interferon & Cytokine Research, 2009
- Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT MethodMethods, 2001