Infect Immun. 2013 Apr;81(4):1306-15. doi: 10.1128/IAI.01304-12. Epub 2013 Feb 4.
Epicutaneous model of community-acquired Staphylococcus aureus skin infections.
Prabhakara R, Foreman O, De Pascalis R, Lee GM, Plaut RD, Kim SY, Stibitz S, Elkins KL, Merkel TJ.
Source
Center for Biologics Evaluation and Research, FDA, Bethesda, Maryland, USA.
Abstract
Staphylococcus 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-γ), interleukin-12 (IL-12) p70, tumor necrosis factor alpha (TNF-α), 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.
PMID: 23381997 [PubMed - indexed for MEDLINE] PMCID: PMC3639601 [Available on 2013/10/1]
PMEU (Portable Microbe Enrichment Unit), for example, see Samgina et al. Journal of Proteome Research, a recent article.
@Elias Hakalehto, thank you for advice. The experiments using PMEU method seems near to in vitro assays rather than the in vivo. But anyway it would be usefull for our planned researches.
Nodirali Normakhamatov. Yes, the bacteria are cultivated and followed up in vitro. However, according to our experience, the conditions in there simulate the circumstances that exist in real life. That is a big difference as compared to traditional cultivation methods. In a way you can transfer the in vivo relationships into the test system in an conceivable way. For example, antibiotic influences or interactions between strains correspond to what happens in vivo. Therefore, we have been able to mimick the conditions from "the bacterial point of view". Of course, all the myriads of impacts from the human host body cannot be integrated into the picture at once. Nevertheless, this often is a benefit, as you may study define the changes in the close proximity of the microbial cells, and the influences of them onto these cells. For an example, I am attaching our recent poster presented at ESPEN (Clinical Nutrition and Metabolism) meeting in Leipzig in the beginning of this September. In that piece of research we were able to make remarkable differences between various probiotic products used in combination with prebiotic flax, onto E.coli and other intestinal bacteria. Consequently, it was possible to have fast validation of the products, with simultaneous demonstration of a strong joint effect of pre- and probiotics. This is about the first time we get relatively direct information on the effect of the probiotics on other bacteria in real-time.
Dear Elias Hakalehto, thank you very much for your explanation and your suggestion. The PMEU model is good news for me. Its very kind from your side that you have shared your experience on it.
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