debridement increases survival in a mouse model of subcutaneous anthrax清创术增加皮下炭疽的生存在一个小鼠模型.pdf

Debridement Increases Survival in a Mouse Model of Subcutaneous Anthrax 1 2 2 1 2 Zachary P. Weiner , Anne E. Boyer , Maribel Gallegos-Candela , Amber N. Cardani , John R. Barr , Ian J. Glomski1* 1 Department of Microbiology, University of Virginia, Charlottesville, Virginia, United States of America, 2 National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America Abstract Anthrax is caused by infection with Bacillus anthracis, a spore-forming Gram-positive bacterium. A major virulence factor for B. anthracis is an immunomodulatory tripartite exotoxin that has been reported to alter immune cell chemotaxis and activation. It has been proposed that B. anthracis infections initiate through entry of spores into the regional draining lymph nodes where they germinate, grow, and disseminate systemically via the efferent lymphatics. If this model holds true, it would be predicted that surgical removal of infected tissues, debridement, would have little effect on the systemic dissemination of bacteria. This model was tested through the development of a mouse debridement model. It was found that removal of the site of subcutaneous infection in the ear increased the likelihood of survival and reduced the quantity of spores in the draining cervical lymph nodes (cLN). At the time of debridement 12 hours post-injection measurable levels of exotoxins were present in the ear, cLN, and serum, yet leukocytes within the cLN were activated; countering the concept that exotoxins inhibit the early inflammatory response to promote bacterial growth. We conclude that the initial entry of spores into the draining lymph node of cutaneous infections alone is no