Dataset Information

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.

SUBMITTER: Liang X

PROVIDER: S-EPMC4929452 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Involvement of the pagR gene of pXO2 in anthrax pathogenesis.

Liang Xudong X Zhang Enmin E Zhang Huijuan H Wei Jianchun J Li Wei W Zhu Jin J Wang Bingxiang B Dong Shulin S

Scientific reports 20160701

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 the ...[more]

PMID: 27363681

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Project description:Genes involved in formation/development of the adenohypophysis, CTNNB1 gene, and microRNAs might be implicated in the craniopharyngioma pathogenesis. The objective of this study is to perform the molecular analysis of HESX1, PROP1, POU1F1, and CTNNB1 genes and evaluate a panel of miRNA expression in craniopharyngioma. We also verified whether the presence of CTNNB1 mutation is associated with clinical findings and miRNA expression. The study included 16 patients with adamantinomatous craniopharyngioma (nine children and seven adults; eight females and eight males; 6-55 years, median 15.5 years). DNA, RNA, and cDNA were obtained from craniopharyngioma and normal pituitaries. DNA was also extracted from peripheral blood of healthy subjects. All genes were amplified by polymerase chain reaction and direct sequenced. Relative quantification of miRNA expression was calculated using the 2(-ΔΔCt) method. We found no mutations in HESX1, PROP1, and POU1F1 genes and four polymorphisms in PROP1 gene which were in Hardy-Weinberg equilibrium and had similar allelic frequencies in craniopharyngioma and controls. We found seven different mutations in CTNNB1 in eight of 16 patients. Younger patients presented more frequently CTNNB1 mutation than adults. We observed hyperexpression of miR-150 (1.7-fold); no different expression of miR-16-1, miR-21, and miR23a; and an underexpression of miR-141, let-7a, miR-16, miR-449, miR-145, miR-143, miR-23b, miR-15a, and miR-24-2 (ranging from -7.5 to -2.5-fold; p = 0.02) in craniopharyngioma. There was no association between tumor size or the recurrence and the presence of CTNNB1mutations. miR-16 and miR-141 were underexpressed in craniopharyngioma presenting CTNNB1 mutations. miR-23a and miR24-2 were hyperexpressed in patients who underwent only one surgery. Mutations or polymorphisms in pituitary transcription factors are unlikely to contribute to the adamantinomatous craniopharyngioma pathogenesis, differently of CTNNB1 mutations. Our data suggest the potential involvement of the deregulation of miRNA expression in the craniopharyngioma pathogenesis and outcome and also that the miRNA could modulate the Wnt signaling pathway in craniopharyngioma tumorigenesis.

Dataset Information

Involvement of the pagR gene of pXO2 in anthrax pathogenesis.

Publications

Involvement of the pagR gene of pXO2 in anthrax pathogenesis.

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