Bacillus anthracis

About: Bacillus anthracis is a research topic. Over the lifetime, 3994 publications have been published within this topic receiving 128122 citations.

Targeting of the BclA and BclB proteins to the Bacillus anthracis spore surface.

Abstract: The exosporium is the outermost layer of the Bacillus anthracis spore. The predominant protein on the exosporium surface is BclA, a collagen-like glycoprotein. BclA is incorporated on the spore surface late in the B. anthracis sporulation pathway. A second collagen-like protein, BclB, has been shown to be surface-exposed on B. anthracis spores. We have identified sequences near the N-terminus of the BclA and BclB glycoproteins responsible for the incorporation of these proteins into the exosporium layer of the spore and used these targeting domains to incorporate reporter fluorescent proteins onto the spore surface. The BclA and BclB proteins are expressed in the mother cell cytoplasm and become spore-associated in a two-step process involving first association of the protein with the spore surface followed by attachment of the protein in a process that involves a proteolytic cleavage event. Protein domains associated with each of these events have been identified. This novel targeting system can be exploited to incorporate foreign proteins into the exosporium of inactivated, spores resulting in the surface display of recombinant immunogens for use as a potential vaccine delivery system.

Anthrax toxins cooperatively inhibit endocytic recycling by the Rab11/Sec15 exocyst

Abstract: Bacillus anthracis is the causative agent of anthrax in humans and other mammals(1,2). In lethal systemic anthrax, proliferating bacilli secrete large quantities of the toxins lethal factor (LF) and oedema factor (EF), leading to widespread vascular leakage and shock. Whereas host targets of LF (mitogen-activated protein-kinase kinases) and EF (cAMP-dependent processes)(3) have been implicated in the initial phase of anthrax(1,2), less is understood about toxin action during the final stage of infection. Here we use Drosophila melanogaster to identify the Rab11/Sec15 exocyst, which acts at the last step of endocytic recycling, as a novel target of both EF and LF. EF reduces levels of apically localized Rab11 and indirectly blocks vesicle formation by its binding partner and effector Sec15 (Sec15-GFP), whereas LF acts more directly to reduce Sec15-GFP vesicles. Convergent effects of EF and LF on Rab11/Sec15 inhibit expression of and signalling by the Notch ligand Delta and reduce DE-cadherin levels at adherens junctions. In human endothelial cells, the two toxins act in a conserved fashion to block formation of Sec15 vesicles, inhibit Notch signalling, and reduce cadherin expression at adherens junctions. This coordinated disruption of the Rab11/Sec15 exocyst by anthrax toxins may contribute to toxin-dependent barrier disruption and vascular dysfunction during B. anthracis infection.

Polyglutamic acid from Bacillus anthracis grown in vivo; structure and aggressin activity.

Abstract: Tomesik & Szongott (1933) obtained a nitrogenous, polysaccharide-free, capsular material from BacillU anthracis which was identified by Ivanovics & Bruckner (1937a, b) as poly-D-glutamic acid. A capsule is formed by virulent strains of B. anthracis and appears to be connected with the aggressive aspect of virulence, that is, with the ability of the pathogen to interfere with the defence mechanisms of the host (for discussion, see Smith & Keppie, 1955). In order to study the connexion of polyglutamic acid with virulence, we have used material produced during growth of the pathogen in vivo when compounds responsible for virulence are necessarily produced. Capsulated organisms were separated from a mixture of plasma and exudate of guinea pigs dying of anthrax (Smith, Keppie & Stanley, 1953). Crude preparations of polyglutamic acid were then obtained from both the organisms and the body fluids (Smith, Zwartouw & HarrisSmith, 1956; Smith & Gallop, 1956). The purification of this polyglutamic acid is described here together with observations on its aggressive activity and structure. Attempts have been made to correlate its biological activity with some physicochemical or structural property. The important structural problem posed by polyglutamic acid is whether the glutamic acid residues are linked by their oc-carboxyl groups (cf. I) or their y-carboxyl groups (cf. II) or both.