title: Novel and unique diagnostic biomarkers for Bacillus anthracis infection.
abstract: A search for bacterium-specific biomarkers in peripheral blood following infection with Bacillus anthracis was carried out with rabbits, using a battery of specific antibodies generated by DNA vaccination against 10 preselected highly immunogenic bacterial antigens which were identified previously by a genomic/proteomic/serologic screen of the B. anthracis secretome. Detection of infection biomarkers in the circulation of infected rabbits could be achieved only after removal of highly abundant serum proteins by chromatography using a random-ligand affinity column. Besides the toxin component protective antigen, the following three secreted proteins were detected in the circulation of infected animals: the chaperone and protease HtrA (BA3660), an NlpC/P60 endopeptidase (BA1952), and a protein of unknown function harboring two SH3 (Src homology 3) domains (BA0796). The three proteins could be detected in plasma samples from infected animals exhibiting 10(3) to 10(5) CFU/ml blood and also in standard blood cultures at 3 to 6 h post-bacterial inoculation at a bacteremic level as low as 10(3) CFU/ml. Furthermore, the three biomarkers appear to be present only in the secretome of B. anthracis, not in those of the related pathogens B. thuringiensis and B. cereus. To the best of our knowledge, this is the first report of direct detection of B. anthracis-specific proteins, other than the toxin components, in the circulation of infected animals.
authors: Department of Biochemistry and Molecular Genetics, Life Science Research Israel Ltd, 2 Ness-Ziona 74100, Israel.
authors: Sagit
authors: S
authors: Sela-Abramovich
authors: Theodor
authors: T
authors: Chitlaru
authors: Orit
authors: O
authors: Gat
authors: Haim
authors: H
authors: Grosfeld
authors: Ofer
authors: O
authors: Cohen
authors: Avigdor
authors: A
authors: Shafferman
mesh_terms: D000818:Animals; D000881:Anthrax / Q000175:diagnosis*; D000942:Antigens, Bacterial / Q000097:blood; D001408:Bacillus anthracis / Q000302:isolation & purification* / Q000378:metabolism*; D001409:Bacillus cereus / Q000378:metabolism; D001413:Bacillus thuringiensis / Q000378:metabolism; D001426:Bacterial Proteins / Q000097:blood*; D001427:Bacterial Toxins / Q000097:blood; D015415:Biomarkers / Q000097:blood; D010450:Endopeptidases / Q000097:blood*; D010949:Plasma / Q000737:chemistry; D011817:Rabbits; D012697:Serine Endopeptidases / Q000097:blood*
chemical_list: D000942:Antigens, Bacterial; C545480:BA0796 protein, Bacillus anthracis; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D015415:Biomarkers; C030325:anthrax toxin; C545479:BA1952 protein, Bacillus anthracis; D010450:Endopeptidases; D012697:Serine Endopeptidases; C545478:htrA protein, Bacillus anthracis