title: Diminished but Not Abolished Effect of Two His351 Mutants of Anthrax Edema Factor in a Murine Model.
abstract: Edema toxin (ET), which is composed of a potent adenylate cyclase (AC), edema factor (EF), and protective antigen (PA), is one of the major toxicity factors of Bacillus anthracis. In this study, we introduced mutations in full-length EF to generate alanine EF(H351A) and arginine EF(H351R) variants. In vitro activity analysis displayed that the adenylyl cyclase activity of both the mutants was significantly diminished compared with the wild-type EF. When the native and mutant toxins were administered subcutaneously in a mouse footpad edema model, severe acute swelling was evoked by wild-type ET, while the symptoms induced by mutant toxins were very minor. Systemic administration of these EF variants caused non-lethal hepatotoxicity. In addition, EF(H351R) exhibited slightly higher activity in causing more severe edema than EF(H351A). Our findings demonstrate that the toxicity of ET is not abolished by substitution of EF residue His351 by alanine or arginine. These results also indicate the potential of the mouse footpad edema model as a sensitive method for evaluating both ET toxicity and the efficacy of candidate therapeutic agents.
authors: Laboratory of Vaccine and Antibody Engineering, Beijing Institute of Biotechnology, Beijing 100071, China. tracyztr@163.com.
authors: Taoran
authors: T
authors: Zhao
authors: Laboratory of Vaccine and Antibody Engineering, Beijing Institute of Biotechnology, Beijing 100071, China. xinghui_zhao@163.com.
authors: Xinghui
authors: X
authors: Zhao
authors: Laboratory of Vaccine and Antibody Engineering, Beijing Institute of Biotechnology, Beijing 100071, China. 18701522421@163.com.
authors: Ju
authors: J
authors: Liu
authors: Laboratory of Vaccine and Antibody Engineering, Beijing Institute of Biotechnology, Beijing 100071, China. myy316@163.com.
authors: Yingying
authors: Y
authors: Meng
authors: Department of Colorectal Surgery, the Second Artillery General Hospital, Beijing 100088, China. fyy19811120@163.com.
authors: Yingying
authors: Y
authors: Feng
authors: Laboratory of Vaccine and Antibody Engineering, Beijing Institute of Biotechnology, Beijing 100071, China. fangting1008vip@163.com.
authors: Ting
authors: T
authors: Fang
authors: Laboratory of Vaccine and Antibody Engineering, Beijing Institute of Biotechnology, Beijing 100071, China. zjl0679@163.com.
authors: Jinlong
authors: J
authors: Zhang
authors: Laboratory of Vaccine and Antibody Engineering, Beijing Institute of Biotechnology, Beijing 100071, China. yangxiuxu118@163.com.
authors: Xiuxu
authors: X
authors: Yang
authors: Laboratory of Vaccine and Antibody Engineering, Beijing Institute of Biotechnology, Beijing 100071, China. lijmqz@126.com.
authors: Jianmin
authors: J
authors: Li
authors: Laboratory of Vaccine and Antibody Engineering, Beijing Institute of Biotechnology, Beijing 100071, China. xujunjie@sina.com.
authors: Junjie
authors: J
authors: Xu
authors: Laboratory of Vaccine and Antibody Engineering, Beijing Institute of Biotechnology, Beijing 100071, China. cw0226@foxmail.com.
authors: Wei
authors: W
authors: Chen
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics* / Q000378:metabolism / Q000633:toxicity*; D001427:Bacterial Toxins / Q000235:genetics* / Q000378:metabolism / Q000633:toxicity*; D016466:CHO Cells; D003412:Cricetulus; D000242:Cyclic AMP / Q000378:metabolism; D004195:Disease Models, Animal; D004487:Edema / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005528:Foot / Q000473:pathology; D006639:Histidine / Q000235:genetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008810:Mice, Inbred C57BL; D009154:Mutation
chemical_list: D000942:Antigens, Bacterial; D001427:Bacterial Toxins; C030325:anthrax toxin; D006639:Histidine; D000242:Cyclic AMP; D000262:Adenylyl Cyclases
keywords: anthrax toxin; edema factor; evaluation model