title: Involvement of the pagR gene of pXO2 in anthrax pathogenesis.
abstract: Anthrax is a disease caused by Bacillus anthracis. Specifically, the anthrax toxins and capsules encoded by the pXO1 and pXO2 plasmids, respectively, are the major virulence factors. We previously reported that the pXO1 plasmid was retained in the attenuated strain of B. anthracis vaccine strains even after subculturing at high temperatures. In the present study, we reinvestigate the attenuation mechanism of Pasteur II. Sequencing of pXO1 and pXO2 from Pasteur II strain revealed mutations in these plasmids as compared to the reference sequences. Two deletions on these plasmids, one each on pXO1 and pXO2, were confirmed to be unique to the Pasteur II strain as compared to the wild-type strains. Gene replacement with homologous recombination revealed that the mutation in the promoter region of the pagR gene on pXO2, but not the mutation on pXO1, contributes to lethal levels of toxin production. This result was further confirmed by RT-PCR, western blot, and animal toxicity assays. Taken together, our results signify that the attenuation of the Pasteur II vaccine strain is caused by a mutation in the pagR gene on its pXO2 plasmid. Moreover, these data suggest that pXO2 plasmid encoded proteins are involved in the virulence of B. anthracis.
authors.affiliation: National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, State Key Laboratory for Infectious Disease Prevention and Control, 102206, Beijing, China.
authors.forename: Xudong
authors.initials: X
authors.lastname: Liang
authors.affiliation: National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, State Key Laboratory for Infectious Disease Prevention and Control, 102206, Beijing, China.
authors.forename: Enmin
authors.initials: E
authors.lastname: Zhang
authors.affiliation: National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, State Key Laboratory for Infectious Disease Prevention and Control, 102206, Beijing, China.
authors.forename: Huijuan
authors.initials: H
authors.lastname: Zhang
authors.affiliation: National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, State Key Laboratory for Infectious Disease Prevention and Control, 102206, Beijing, China.
authors.forename: Jianchun
authors.initials: J
authors.lastname: Wei
authors.affiliation: National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, State Key Laboratory for Infectious Disease Prevention and Control, 102206, Beijing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Huadong Medical Institute of Biotechniques, 210002, Nanjing, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Lanzhou Institute of Biological Products Co. Ltd, 730046, Lanzhou, China.
authors.forename: Bingxiang
authors.initials: B
authors.lastname: Wang
authors.affiliation: Lanzhou Institute of Biological Products Co. Ltd, 730046, Lanzhou, China.
authors.forename: Shulin
authors.initials: S
authors.lastname: Dong
mesh_terms: D000818:Animals; D000881:Anthrax / Q000821:virology; D000942:Antigens, Bacterial / Q000235:genetics / Q000378:metabolism; D001408:Bacillus anthracis / Q000235:genetics* / Q000378:metabolism / Q000472:pathogenicity; D001426:Bacterial Proteins / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D001427:Bacterial Toxins / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D008297:Male; D008807:Mice, Inbred BALB C; D009154:Mutation; D010957:Plasmids / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D012097:Repressor Proteins / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D017422:Sequence Analysis, DNA; D016019:Survival Analysis; D014774:Virulence / Q000235:genetics
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D004269:DNA, Bacterial; C548703:PagR protein, Bacillus anthracis; D012097:Repressor Proteins; C030325:anthrax toxin