Bacillus anthracis (B. anthracis) has become one of the greatest biological warfare threats to mankind due to its high morbidity and mortality. The ability of antibiotics to control B. anthracis populations is limited, so finding a novel and effective B. anthraci antagonist is becoming necessary. With comprehensive knowledge about phage and B. anthracis, Creative Biolabs provides support for the development of therapeutic phage against B. anthracis.
B. anthracis is a gram-positive bacillus about 1-6 μm in length. The bacteria exist in soil in form of endospores. B. anthracis in such form is extremely resistant to harsh environments and can survive for decades. After being ingested by animals, the spores may replicate in livestock and cause death. Native B. anthracis also infects humans and causes anthrax, usually accompanied by necrotic lesions on the face, hands, and neck. B. anthracis infections are often fatal without proper treatment.
Fig.1 B. anthracis grown on agar. (Duery, 2014)
In general, B. anthracis is sensitive to common antibiotics such as penicillin, vancomycin, and tetracycline, but penicillin-resistant strains have also been found. Treatment of B. anthracis infection with broad-spectrum antibiotics or antitoxins is feasible. However, intravenous antibiotic therapy can take longer to achieve a cure. Strains used for phage studies typically include B. anthracis 34F2, DS201579, Bacillus subtilis ATCC 6633, Bacillus cereus ATCC 33019.
Fig.2 Stained blood smear of B. anthracis. (Hassim, 2020)
The virulence of B. anthracis is responsible by the typical virulence plasmids pXO1 and pXO2. The pXO1 plasmid encodes major virulence factors, including the protective antigen pag, lethal factor lef and edema factor cya. Lef and pag make up the lethal toxin, while edema toxin is a combination of cya and pag. The lethal factor causes macrophages to produce a large amount of TNF-α and IL-1β, eventually leading to septic shock, ischemic shock, and even death. pXO2 is responsible for encoding weakly immunogenic and antiphagocytic protein capsules with poly-D-gamma-glutamic acid as the main component. poly-D-gamma-glutamic acid creates a negative charge that protects the bacteria from being attacked by the host immune system or complement. This unique protective capsule provides an evolutionary advantage for B. anthracis to survive in the host.
The genetic data of more than 400 Bacillus phages have been extracted and preserved, including phage γ, Wip1, AP50c, J5a, F16Ba, z1a, etc. The host specificity of B. anthracis phages is generally determined by receptor-binding proteins (RBP) located in the tail (Siphorviridae) or head (Tectiviridae) fibers. Phage recognition and adsorption sites can be polysaccharides, teichoic acids, structural or capsule proteins. The B. anthracis receptor protein GamR and the surface protein Sap, AP50c have been identified as recognition sites for some specific types of phages. After the synthesis of progeny virions by the bacterial host, Bacillus phage cleaves the peptidoglycan cell wall of the infected bacteria via endolysin or holin and releases progeny phages.
Fig.3 Binding of RBP to Bacillus anthracis. (Braun, 2020)
Due to the actual or potential threat posed by B. anthracis to humans, the development of phage formulations for the treatment of human and animal infections or as disinfectants is of great practical interest. Creative Biolabs currently provides reliable novel phage-related services for B. anthracis. Our professionals are ready to answer your questions that you may encounter during your research and development process. Please do not hesitate to contact us for more information.
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