A Murine Skin Infection Model Capable of Differentiating the Dermatopathology of Community-Associated MRSA Strain USA300 from Other MRSA Strains.

Glen Armstrong,Sameer Elsayed,Kunyan Zhang,Kaiyu Wu,John Conly,Duane Barber,Bjӧrn Petri,Jack Zhang,JoAnn McClure

doi: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.

Highlights

Methicillin-resistant Staphylococcus aureus (MRSA) is a leading cause of infection worldwide
Phenotypic tests indicated that USA400-CMRSA7 was sensitive to erythromycin and ciprofloxacin, unlike USA300-C2406, which was resistant to both
M92 was resistant to clindamycin, gentamicin, and tetracycline, while USA300-C2406 was sensitive to these agents

Summary

Introduction

Methicillin-resistant Staphylococcus aureus (MRSA) is a leading cause of infection worldwide. It was traditionally considered a nosocomial pathogen in healthcare facilities (known as hospital-associated MRSA (HA-MRSA)). Community-associated MRSA (CAMRSA) emerged in the 1990s, and quickly increased and replaced HA-MRSA in the United States and Canada. Prior to 2000, the predominant CA-MRSA strain in North America was pulsotype USA400 (ST1-MRSA-IV). It was quickly replaced by pulsotype USA300. (ST8-MRSA-IV), which is the strain responsible for the increase in CA-MRSA infections in North America [1,2], as well as globally [3,4,5]. USA300 causes primarily acute bacterial skin and skin structure infections (ABSSSIs) [6], with an estimated 44.6% of ABSSSIs in

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Discussion

Conclusion