Bacillus anthracis, lethal factor

Bernard , L., Vitale, G., Montecucco, C., Musacchio, A. (2000). Expression, crystallization and preliminary X-ray diffraction studies of recombinant Bacillus anthracis lethal factor. Acta Crystallogr. D. Biol. Crystallogr. 56(Pt 11) 1449-51. 

Kochi, S.K., Schiavo, G., Mock, M., Montecucco, C. (1994). Zinc content of the Bacillus anthracis lethal factor. FEMS Microbiol. Lett. 124 343-8. 

The anthrax bioterrorist attacks that followed the events of September 11th 2001 resulted in a renewed interest BadUus anthracis, the causative agent of this disease. Research has focused on the development of better vaccines than the one currently available. It has been estimated that the aerosolized release of 100 kg of anthrax spores upwind of Washington DC would cause mortalities of 130,000-3,000,000 [63]. Nonetheless, wild-type Bacillus anthracis is susceptible to conventional antibiotics, including penicillin, oxyfloxacin and ciprofloxacin. The problem lies not with the bacterial infection itself, but with three proteins released by the bacteria - protective antigen (PA, 83 kDa), lethal factor (LF, 90 kDa) and edema factor (EF, 89 kDa) -known as anthrax toxins [63]. 

Very recently the protein structures of ACE with the bound inhibitors Lisinopril (Fig. 4) and Captopril were published (101,102). Also the protein structure of the LF from Bacillus anthracis (PDB-Code 1J7N) caused a sensation, which is now available to the public (Fig. 14b) (103). LF is part of the toxic exotoxin complex composed of three distinct proteins (protective antigen PA, the lethal factor LF and the edema factor EF), and is thought to be the most toxic... 

Fig. 14. Active site (a) of the angiotensin converting enzyme (ACE) with Lisinopril inhibitor bound to zinc(II) (PDB-Code 1086) (101), (b) of the lethal factor of Bacillus anthracis (PDB-Code 1J7N) (103).

Anthrax toxin is a bacterial toxin from Bacillus anthracis consisting of three parts protective antigen (PA), lethal factor (LF) and edema factor (EF). Both LF and EF compete for binding sites on the PA protein. The PA protein binds with high affinity to an as yet unknown receptor on macrophages and related cell types. When PA is internalized by the target cells, it functions as a shuttle protein for either EF or LF. Intracellularly, in the acidic environment of the endosome, EF and LF are capable of entering the cytosol by pH-dependent pore formation [139]. 

Smith, H., Keppie, J. (1954). Observations on experimental anthrax demonstration of a specific lethal factor produced in vivo by Bacillus anthracis. Nature 173 869-70. 

In other instances, where analyte-sensitive dyes with a narrower Stokes shift are utilized, the contribution of the long-wavelength EL tail to the background can be large, reducing the detection sensitivity and deteriorating the LOD. An example for that behavior is that of a sensor for anthrax lethal factor (LF), which is one of the three proteins of the anthrax toxin secreted by the live Bacillus anthracis bacterium. The development of a compact, field-deployable, and low-cost sensor for prompt, on-site detection of... 

Burroughs-Tencza, S. FRET-based peptide biosensors for detecting anthrax lethal factor protease and Bacillus anthracis. PCT Int. Appl. WO 2001059149, 2001 Chem. Abstr. 2001, 135, 177260. 

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