Hahn BL, Onunkwo CC, Watts CJ et al.Systemic dissemination and cutaneous damage in a mouse model of staphylococcal skin infections. Microb Pathog 47:16-23

Division of Infectious Diseases, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI 53226, USA
Microbial Pathogenesis (Impact Factor: 1.79). 07/2009; 47(1):16-23. DOI: 10.1016/j.micpath.2009.04.007


Serious staphylococcal infections frequently begin in the skin. The present study used a mouse model of such infections to evaluate the ability of Staphylococcus aureus to disseminate from the skin and to determine if cutaneous damage from the infections was required for dissemination. The mice were inoculated with S. aureus onto flank skin prepared by a tape-stripping method that caused minimal disruption of the epidermal keratinocyte layers. After these inoculations the staphylococci were found to disseminate to the spleen and kidneys of almost all animals within 6 h. Induction of leucopenia did not affect this process. Cutaneous damage was prominent in these experimental infections and included loss of the epidermis, neutrophil infiltration into the epidermis, and complete necrosis of the dermis. The latter also occurred in cyclophosphamide-treated animals, indicating that the organisms themselves and not the host inflammatory responses were responsible. Dermal necrosis did not develop until 48 h after inoculation, a time by which dissemination had already occurred. Therefore, in this mouse model system S. aureus is capable of penetrating the epidermal keratinocyte layers and disseminating rapidly after inoculation; the experimental infections do produce significant dermal damage, but the latter develops after dissemination has already taken place.

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Available from: Beth L Hahn, Oct 28, 2014
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    • "Depletion of immune cells via specific monoclonal antibodies (anti-Ly6G) or chemotherapy (cyclophosphamide) causes a dramatic reduction in the challenge dose required for skin infection (Kraft et al., 1986; Molne et al., 2000). In contrast to immune-competent mice, leukopenic mice cannot contain staphylococci in the skin and develop systemic infections with rapidly lethal outcome (Hahn et al., 2009). Similar observations have been made in humans, where iatrogenic leukopenia or hereditary defects in the NADPH oxidase or in the respiratory burst of myeloid cells are associated with increased susceptibility towards S. aureus infection (Heyworth et al., 2003). "
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    ABSTRACT: Staphylococcus aureus - a commensal of the human skin, nares and gastrointestinal tract - is also a leading cause of bacterial skin and soft tissue infection (SSTIs), bacteremia, sepsis, peritonitis, pneumonia and endocarditis. Antibiotic-resistant strains, designated MRSA (methicillin-resistant S. aureus), are common and represent a therapeutic challenge. Current research and development efforts seek to address the challenge of MRSA infections through vaccines and immune therapeutics. Mice have been used as experimental models for S. aureus SSTI, bacteremia, sepsis, peritonitis and endocarditis. This work led to the identification of key virulence factors, candidate vaccine antigens or immune-therapeutics that still require human clinical testing to establish efficacy. Past failures of human clinical trials raised skepticism whether the mouse is an appropriate model for S. aureus disease in humans. S. aureus causes chronic-persistent infections that, even with antibiotic or surgical intervention, reoccur in humans and in mice. Determinants of S. aureus evasion from human innate and adaptive immune responses have been identified, however only some of these are relevant in mice. Future research must integrate these insights and refine the experimental mouse models for specific S. aureus diseases to accurately predict the failure or success for candidate vaccines and immune-therapeutics.
    Journal of immunological methods 04/2014; 410. DOI:10.1016/j.jim.2014.04.007 · 1.82 Impact Factor
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    • "Each of the 3 may be involved at times. In our earlier studies, free bacteria were often found in dermis underneath intact keratinocyte layers [2], suggesting a similar translocation process in the skin. "
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    ABSTRACT: Background: Staphylococcus aureus can invade the bloodstream and cause bacteremic infections, but this organism frequently produces serious deep infections without bacteremia or an identifiable portal of entry. Methods: We used experimental cutaneous S. aureus infections in mice to determine if the bacteria could reach deep organs without travel through the bloodstream. Results: After skin surface application the bacteria rapidly distributed to lymph nodes, spleen, kidneys and other organs. In these animals, blood cultures were negative, dissemination was more efficient after surface application than injection near dermal blood vessels, and kidney bacterial localization sites were unlike those of bacteremic infections. Whereas normal mice eventually cleared bacteria from the deep sites, those with prolonged immunosuppression became moribund from these infections; they also had negative blood cultures and kidney localization not consistent with hematogenous dissemination. Bacteria were also found in the intervening abdominal wall outside the spleen and kidney sites, suggesting direct movement of the organisms from the skin surface through connecting tissues. Conclusions: Although capable of hematogenous dissemination, S. aureus can also spread from skin to deep organs by a non-bacteremic process. In this case the bacteria appear to migrate directly from the skin surface to the deep organs below.
    Microbial Pathogenesis 06/2013; 63. DOI:10.1016/j.micpath.2013.05.012 · 1.79 Impact Factor
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    • "Skin and connective tissue sections from the inoculated area and spleen and liver of each animal were removed aseptically , weighed and homogenized in tissue homogenizers. CFU (colony forming units)/g of tissue was determined by plating serial dilution on MH (Müller Hinton) broth media (2.0 g/L beef extract powder, 17.5 g/L acid digest of casein and 1.5 g/L starch).The systemic dissemination of MRSA was evaluated in cultures of spleen and kidney (Hahn et al., 2009). "
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    ABSTRACT: Acanthospermal B (AcB), the major sesquiterpene lactone (SL) of Acanthospermum hispidum, an herb widely spread in Argentina, is a selective antibacterial agent against Enterococcus faecalis and Staphylococcus aureus, but inactive on Gram-negative and Lactobacillus. Methicillin-resistant Staphylococcus aureus (MRSA) is one of the main microorganisms involved in human chronic infection. A balb\c mouse skin infection model was developed to reproduce the lesions caused by acute and chronic infections produced by MRSA. After determination of the maximum concentration of AcB unable to produce tissular injury after intradermal injection, the anti-MRSA effect of AcB was evaluated on skin, liver and spleen tissues of infected mice. AcB, at doses of 2.5 mg/kg, produced a ten times decrease of MRSA growth in skin infection. In addition, the same dose prevented the dissemination to liver and/or spleen. AcB also displayed a bacteriostatic effect, in vitro, on MRSA cultures at 50 µg/mL that seems to be caused by partial denaturation of total bacterial DNA and/or inhibition of the PCR reaction in not denaturized DNA. Finally, total MRSA cell wall lysis occurred at a concentration of 100 µg/mL of AcB after 2 h of exposure.
    Phytotherapy Research 04/2011; 25(4):597-602. DOI:10.1002/ptr.3300 · 2.66 Impact Factor
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