Analysis of epidermal entry in experimental cutaneous Bacillus anthracis infections in mice
ABSTRACT Cutaneous infection is the most common form of human anthrax, but little is known of Bacillus anthracis-epidermal interactions. To study the latter, we used experimental inoculations of B. anthracis Sterne spores onto mouse flank skin. In DBA/2 mice (a sensitive strain) 10(7) spores injected intradermally or applied under occlusive dressings to abraded skin produced ipsilateral inguinal edema and rapid death. Epicutaneous application to shaved-only skin produced edema and death in most animals, but at longer times. Mortality after inoculation onto abraded skin was less in C57BL/6 mice (a relatively resistant strain). Inoculations onto shaved-only skin immunized C57BL/6 mice, and they survived later intradermal spore injections. Histology revealed massive organism proliferation in remaining epidermis and hair follicles of inoculated abraded skin, but less growth in the dermis itself. Conversely, no foci could be located by microscopic examination after inoculation onto shaved-only skin. High-dose nonocclusive dressing inoculations onto unshaved skin in DBA/2 mice revealed small numbers of infective foci, all in hair follicles. These results suggest that epidermal damage may increase infection susceptibility to B. anthracis of hair follicle contents and remaining epidermal remnants; the findings also indicate that access may occur through hair follicles and the denuded dermis.
SourceAvailable from: Agata Bielawska-Drózd[Show abstract] [Hide abstract]
ABSTRACT: Articles concerning new aspects of B. anthracis mechanisms of infection were reviewed. It was found, that the hair follicle plays an important role in the spore germination process. The hair follicle represent an important portal of entry in the course of the cutaneous form of disease infections. After mouse exposition to aerosol of spores prepared from B. anthracis strains, an increase in the level of TNF-α cytokines was observed. The TNF-α cytokines were produced after intrusion into the host by the microorganism. This process may play a signi cant role in the induced migration of infected cells APCs (Antigen Presenting Cells) via chemotactic signals to the lymph nodes. It was explained that IgG, which binds to the spore surface, activates the adaptive immune system response. As a result, the release C3b opsonin from the spore surface, and mediating of C3 protein fragments of B. anthracis spores phagocytosis by human macrophages, was observed. The genes coding germination spores protein in mutant strains of B. anthracis MIGD was a crucial discovery. According to this, it could be assumed that the activity of B. anthracis spores germination process is dependent upon the sleB, cwlJ1 and cwlJ2 genes, which code the GSLEs lithic enzymes. It was also discovered that the speci c antibody for PA20, which binds to the PA20 antigenic determinant, are able to block further PA83 proteolytic ssion on the surface of cells. This process neutralized PA functions and weakened the activity of free PA20, which is produced during the PA83 enzyme ssion process. Interaction between PA63 monomer and LF may be helpful in the PA63 oligomerization and grouping process, and the creation of LF/PA63 complexes may be a part of an alternative process of assembling the anthrax toxin on the surface of cells. It was found that actin-dependent endocytosis plays an important role in the PA heptamerisation process and leads to blocking the toxin activity. Chaperones, a protein derived from host cells, may be helpful in ATP and cytosolic factors translocation, and in this way increase the translocation of diphteria toxin A domein (DTA) and substrate of fusion protein LF(N)-DTA.Annals of agricultural and environmental medicine: AAEM 12/2012; 19(4):613-8. · 3.06 Impact Factor
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ABSTRACT: 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.Microbial Pathogenesis 07/2009; DOI:10.1016/j.micpath.2009.04.007 · 2.00 Impact Factor
Bacillus anthracis and Anthrax, 11/2010: pages 179 - 208; , ISBN: 9780470891193