Epicutaneous Model of Community-Acquired Staphylococcus aureus Skin Infections

Abstract

bStaphylococcus aureus is one of the most common etiological agents of community-acquired skin and soft tissue infection (SSTI). Although the majority of S. aureus community-acquired SSTIs are uncomplicated and self-clearing in nature, some percentage of these cases progress into life-threatening invasive infections. Current animal models of S. aureus SSTI suffer from two drawbacks: these models are a better representation of hospital-acquired SSTI than community-acquired SSTI, and they involve methods that are difficult to replicate. For these reasons, we sought to develop a murine model of community-acquired methicillin-resistant S. aureus SSTI (CA-MRSA SSTI) that can be consistently reproduced with a high degree of precision. We utilized this model to begin to characterize the host immune response to this type of infection. We infected mice via epicutaneous challenge of the skin on the outer ear pinna using Morrow-Brown allergy test needles coated in S. aureus USA300. When mice were challenged in this model, they developed small, purulent, self-clearing lesions with predictable areas of inflammation that mimicked a human infection. CFU in the ear pinna peaked at day 7 before dropping by day 14. The T h 1 and T h 17 cytokines gamma interferon (IFN-␥), interleukin-12 (IL-12) p70, tumor necrosis factor alpha (TNF-␣), IL-17A, IL-6, and IL-21 were all significantly increased in the draining lymph node of infected mice, and there was neutrophil recruitment to the infection site. In vivo neutrophil depletion demonstrated that neutrophils play a protective role in preventing bacterial dissemination and fatal invasive infection.

The adherens junctions control susceptibility to Staphylococcus aureus α-toxin

“…In this model, S. aureus is superficially introduced into the ear pinnae using a shallow needle, resulting in a necrotic, inflammatory lesion that resolves with tissue loss (37). Confirming the importance of α-toxin for this infection, USA300 LAC hla::ermB isogenic mutant infections result in significantly decreased lesion size compared with WT USA300 LAC (Fig.…”

“…Murine models of MRSA superficial skin and pneumonia infections were carried out as previously described (7,8,37) with minor modifications. Inoculum preparation, infection conditions, and postinfection procedures are fully presented in SI Materials and Methods.…”

Nonredundant Roles of Interleukin-17A (IL-17A) and IL-22 in Murine Host Defense against Cutaneous and Hematogenous Infection Due to Methicillin-Resistant Staphylococcus aureus

“…A frequent complication of invasive MRSA infections is hematogenous seeding of target organs, such as the kidney (38,39). Thus, the kidney CFU burden was measured at 7 days postinfection to assess the extent of hematogenous dissemination.…”

O modelo de infecção intradérmica por Staphylococcus aureus: uma alternativa para o entendimento do recrutamento de células para o sítio de infecção?

“…Neste caso, o infiltrado localizado de neutrófilos sugere que estas células desempenham um papel importante no controle da infecção. Para demonstrar que estes polimorfonucleares desempenham um papel importante na depuração bacteriana em infecções causadas por S. aureus, Prabhakara et al, (2013) [25], mostrou que a depleção destes leucócitos in vivo leva a extensas áreas de necrose no sitio da infecção (orelha), aumentando a gravidade da lesão, o que não é observado em animais não neutropênicos. Além disso, a taxa de sobrevivência pós-infecção é menor nos em animais que tiveram os neutrófilos depletados.…”

“…Esta hiperplasia ocorre provavelmente pelo aumento de diferentes populações de células imunes. Prabhakara et al, (2013) [25] mostrou após a infecção por S. aureus há um aumento de células B, células TCD4+, células TCD8+, células dendríticas, células natural killer e polimorfonucleares no linfonodo drenante da lesão. Os resultados mostram que a imunização prévia de animais ao S. aureus inativado tem provavelmente um efeito protetor em resposta a um desafio posterior com a bactéria viva e virulenta.…”