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Toxins 2016, 8(2), 35; doi:10.3390/toxins8020035

Diminished but Not Abolished Effect of Two His351 Mutants of Anthrax Edema Factor in a Murine Model

1
Laboratory of Vaccine and Antibody Engineering, Beijing Institute of Biotechnology, Beijing 100071, China
2
Department of Colorectal Surgery, the Second Artillery General Hospital, Beijing 100088, China
*
Authors to whom correspondence should be addressed.
Academic Editor: Shihui Liu
Received: 28 October 2015 / Revised: 8 January 2016 / Accepted: 15 January 2016 / Published: 2 February 2016
(This article belongs to the Collection Anthrax Toxins)
View Full-Text   |   Download PDF [4293 KB, uploaded 2 February 2016]   |  

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. View Full-Text
Keywords: anthrax toxin; edema factor; evaluation model anthrax toxin; edema factor; evaluation model
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MDPI and ACS Style

Zhao, T.; Zhao, X.; Liu, J.; Meng, Y.; Feng, Y.; Fang, T.; Zhang, J.; Yang, X.; Li, J.; Xu, J.; Chen, W. Diminished but Not Abolished Effect of Two His351 Mutants of Anthrax Edema Factor in a Murine Model. Toxins 2016, 8, 35.

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