Recombinant HSA-CMG2 Is a Promising Anthrax Toxin Inhibitor
Anthrax toxin is the major virulence factor produced by Bacillus anthracis. Protective antigen (PA) is the key component of the toxin and has been confirmed as the main target for the development of toxin inhibitors. The inhibition of the binding of PA to its receptor, capillary morphogenesis protei...
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| Format: | Article |
| Language: | English |
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MDPI AG
2016-01-01
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| Series: | Toxins |
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| Online Access: | http://www.mdpi.com/2072-6651/8/1/28 |
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| author | Liangliang Li Qiang Guo Ju Liu Jun Zhang Ying Yin Dayong Dong Ling Fu Junjie Xu Wei Chen |
| author_facet | Liangliang Li Qiang Guo Ju Liu Jun Zhang Ying Yin Dayong Dong Ling Fu Junjie Xu Wei Chen |
| author_sort | Liangliang Li |
| collection | DOAJ |
| description | Anthrax toxin is the major virulence factor produced by Bacillus anthracis. Protective antigen (PA) is the key component of the toxin and has been confirmed as the main target for the development of toxin inhibitors. The inhibition of the binding of PA to its receptor, capillary morphogenesis protein-2 (CMG2), can effectively block anthrax intoxication. The recombinant, soluble von Willebrand factor type A (vWA) domain of CMG2 (sCMG2) has demonstrated potency against anthrax toxin. However, the short half-life of sCMG2 in vivo is a disadvantage for its development as a new anthrax drug. In the present study, we report that HSA-CMG2, a protein combining human serum albumin (HSA) and sCMG2, produced in the Pichia pastoris expression system prolonged the half-life of sCMG2 while maintaining PA binding ability. The IC50 of HSA-CMG2 is similar to those of sCMG2 and CMG2-Fc in in vitro toxin neutralization assays, and HSA-CMG2 completely protects rats from lethal doses of anthrax toxin challenge; these same challenge doses exceed sCMG2 at a sub-equivalent dose ratio and overwhelm CMG2-Fc. Our results suggest that HSA-CMG2 is a promising inhibitor of anthrax toxin and may contribute to the development of novel anthrax drugs. |
| first_indexed | 2024-12-10T07:35:05Z |
| format | Article |
| id | doaj.art-58b06bcc27e14989b1f032651e27eb72 |
| institution | Directory Open Access Journal |
| issn | 2072-6651 |
| language | English |
| last_indexed | 2024-12-10T07:35:05Z |
| publishDate | 2016-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Toxins |
| spelling | doaj.art-58b06bcc27e14989b1f032651e27eb722022-12-22T01:57:27ZengMDPI AGToxins2072-66512016-01-01812810.3390/toxins8010028toxins8010028Recombinant HSA-CMG2 Is a Promising Anthrax Toxin InhibitorLiangliang Li0Qiang Guo1Ju Liu2Jun Zhang3Ying Yin4Dayong Dong5Ling Fu6Junjie Xu7Wei Chen8Laboratory of Vaccine and Antibody Engineering, Beijing Institute of Biotechnology, Beijing 100071, ChinaLaboratory of Vaccine and Antibody Engineering, Beijing Institute of Biotechnology, Beijing 100071, ChinaLaboratory of Vaccine and Antibody Engineering, Beijing Institute of Biotechnology, Beijing 100071, ChinaLaboratory of Vaccine and Antibody Engineering, Beijing Institute of Biotechnology, Beijing 100071, ChinaLaboratory of Vaccine and Antibody Engineering, Beijing Institute of Biotechnology, Beijing 100071, ChinaLaboratory of Vaccine and Antibody Engineering, Beijing Institute of Biotechnology, Beijing 100071, ChinaLaboratory of Vaccine and Antibody Engineering, Beijing Institute of Biotechnology, Beijing 100071, ChinaLaboratory of Vaccine and Antibody Engineering, Beijing Institute of Biotechnology, Beijing 100071, ChinaLaboratory of Vaccine and Antibody Engineering, Beijing Institute of Biotechnology, Beijing 100071, ChinaAnthrax toxin is the major virulence factor produced by Bacillus anthracis. Protective antigen (PA) is the key component of the toxin and has been confirmed as the main target for the development of toxin inhibitors. The inhibition of the binding of PA to its receptor, capillary morphogenesis protein-2 (CMG2), can effectively block anthrax intoxication. The recombinant, soluble von Willebrand factor type A (vWA) domain of CMG2 (sCMG2) has demonstrated potency against anthrax toxin. However, the short half-life of sCMG2 in vivo is a disadvantage for its development as a new anthrax drug. In the present study, we report that HSA-CMG2, a protein combining human serum albumin (HSA) and sCMG2, produced in the Pichia pastoris expression system prolonged the half-life of sCMG2 while maintaining PA binding ability. The IC50 of HSA-CMG2 is similar to those of sCMG2 and CMG2-Fc in in vitro toxin neutralization assays, and HSA-CMG2 completely protects rats from lethal doses of anthrax toxin challenge; these same challenge doses exceed sCMG2 at a sub-equivalent dose ratio and overwhelm CMG2-Fc. Our results suggest that HSA-CMG2 is a promising inhibitor of anthrax toxin and may contribute to the development of novel anthrax drugs.http://www.mdpi.com/2072-6651/8/1/28Bacillus anthracisprotective antigenanthrax toxin inhibitorCMG2HSA |
| spellingShingle | Liangliang Li Qiang Guo Ju Liu Jun Zhang Ying Yin Dayong Dong Ling Fu Junjie Xu Wei Chen Recombinant HSA-CMG2 Is a Promising Anthrax Toxin Inhibitor Toxins Bacillus anthracis protective antigen anthrax toxin inhibitor CMG2 HSA |
| title | Recombinant HSA-CMG2 Is a Promising Anthrax Toxin Inhibitor |
| title_full | Recombinant HSA-CMG2 Is a Promising Anthrax Toxin Inhibitor |
| title_fullStr | Recombinant HSA-CMG2 Is a Promising Anthrax Toxin Inhibitor |
| title_full_unstemmed | Recombinant HSA-CMG2 Is a Promising Anthrax Toxin Inhibitor |
| title_short | Recombinant HSA-CMG2 Is a Promising Anthrax Toxin Inhibitor |
| title_sort | recombinant hsa cmg2 is a promising anthrax toxin inhibitor |
| topic | Bacillus anthracis protective antigen anthrax toxin inhibitor CMG2 HSA |
| url | http://www.mdpi.com/2072-6651/8/1/28 |
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