title: The poly-γ-D-glutamic acid capsule of Bacillus anthracis enhances lethal toxin activity.
abstract: The poly-γ-D-glutamic acid (PGA) capsule is one of the major virulence factors of Bacillus anthracis, which causes a highly lethal infectious disease. The PGA capsule disguises B. anthracis from immune surveillance and allows its unimpeded growth in the host. The PGA capsule recently was reported to be associated with lethal toxin (LT) in the blood of experimentally infected animals (M. H. Cho, et al., Infect. Immun. 78:387-392, 2010). The effect of PGA, either alone or in combination with LT, on macrophages, which play an important role in the progression of anthrax disease, has not been thoroughly investigated. In this study, we investigated the effect of PGA on LT cytotoxicity using the mouse macrophage cell line J774A.1. PGA produced a concentration-dependent enhancement of the cytotoxicity of LT on J774A.1 cells through an enhancement in the binding and accumulation of protective antigen to its receptors. The increase of LT activity was confirmed using Western blot analysis, which showed that the combination of PGA and LT produced a greater degree of degradation of mitogen-activated protein kinase kinases and an increased level of the activation of the proform of caspase-1 to its processed form compared to the effects of LT alone. In addition, mice that received a tail vein injection of both PGA and LT had a significantly increased rate of death compared to that of mice injected with LT alone. PGA had no effect when added to cultures or administered to mice in the absence of LT. These results emphasize the importance of PGA in the pathogenesis of anthrax infection.
authors.affiliation: Division of High-Risk Pathogen Research, Center for Infectious Diseases, National Institute of Health, 187 Osongsaengmyeong 2-ro, Cheongwon-gun, Chungbuk 363-951, South Korea.
authors.forename: Jeyoun
authors.initials: J
authors.lastname: Jang
authors.forename: Minhui
authors.initials: M
authors.lastname: Cho
authors.forename: Jeong-Hoon
authors.initials: JH
authors.lastname: Chun
authors.forename: Min-Hee
authors.initials: MH
authors.lastname: Cho
authors.forename: Jungchan
authors.initials: J
authors.lastname: Park
authors.forename: Hee-Bok
authors.initials: HB
authors.lastname: Oh
authors.forename: Cheon-Kwon
authors.initials: CK
authors.lastname: Yoo
authors.forename: Gi-eun
authors.initials: GE
authors.lastname: Rhie
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000633:toxicity*; D001408:Bacillus anthracis / Q000276:immunology / Q000472:pathogenicity*; D016667:Bacterial Capsules / Q000633:toxicity*; D001427:Bacterial Toxins / Q000633:toxicity*; D015153:Blotting, Western; D020170:Caspase 1 / Q000378:metabolism; D002460:Cell Line; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D011099:Polyglutamic Acid / Q000031:analogs & derivatives* / Q000633:toxicity; D037521:Virulence Factors / Q000633:toxicity*
chemical_list: D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D037521:Virulence Factors; C030325:anthrax toxin; C511775:poly(gamma-glutamic acid); D011099:Polyglutamic Acid; D020929:Mitogen-Activated Protein Kinase Kinases; D020170:Caspase 1