title: Deletion mutants of protective antigen that inhibit anthrax toxin both in vitro and in vivo.
abstract: The anthrax toxin complex is primarily responsible for most of the symptoms of anthrax. This complex is composed of three proteins, anthrax protective antigen, anthrax edema factor, and anthrax lethal factor. The three proteins act in binary combination of protective antigen plus edema factor (edema toxin) and protective antigen plus lethal factor (lethal toxin) that paralyze the host defenses and eventually kill the host. Both edema factor and lethal factor are intracellularly acting proteins that require protective antigen for their delivery into the host cell. In this study, we show that deletion of certain residues of protective antigen results in variants of protective antigen that inhibit the action of anthrax toxin both in vitro and in vivo. These mutants protected mice against both lethal toxin and edema toxin challenge, even when injected at a 1:8 ratio relative to the wild-type protein. Thus, these mutant proteins are promising candidates that may be used to neutralize the action of anthrax toxin.
authors.affiliation: Centre for Biotechnology, Jawaharlal Nehru University, New Delhi 110067, India.
authors.forename: Nidhi
authors.initials: N
authors.lastname: Ahuja
authors.forename: Praveen
authors.initials: P
authors.lastname: Kumar
authors.forename: Sheeba
authors.initials: S
authors.lastname: Alam
authors.forename: Megha
authors.initials: M
authors.lastname: Gupta
authors.forename: Rakesh
authors.initials: R
authors.lastname: Bhatnagar
mesh_terms: D000818:Animals; D000881:Anthrax / Q000517:prevention & control*; D000942:Antigens, Bacterial; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism / Q000633:toxicity; D001427:Bacterial Toxins / Q000037:antagonists & inhibitors* / Q000235:genetics* / Q000633:toxicity; D016466:CHO Cells; D002460:Cell Line; D006224:Cricetinae; D051379:Mice; D008807:Mice, Inbred BALB C; D016297:Mutagenesis, Site-Directed; D017384:Sequence Deletion
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D001427:Bacterial Toxins; C030325:anthrax toxin