Bacterial toxins: a table of lethal amounts.

The dormant and durable spore form of Bacillus anthracis is an ideal biological weapon of mass destruction. Once inhaled, spores are transported by alveolar macrophages to lymph nodes surrounding the lungs, where they germinate; subsequent vegetative expansion causes an overwhelming flood of bacteria and toxins into the blood, killing up to 99% of untreated victims. Natural and genetically engineered antibiotic-resistant bacilli amplify the threat of spores being used as weapons, and heighten the need for improved treatments and spore-detection methods after an intentional release. We exploited the inherent binding specificity and lytic action of bacteriophage enzymes called lysins for the rapid detection and killing of B. anthracis. Here we show that the PlyG lysin, isolated from the gamma phage of B. anthracis, specifically kills B. anthracis isolates and other members of the B. anthracis 'cluster' of bacilli in vitro and in vivo. Both vegetative cells and germinating spores are susceptible. The lytic specificity of PlyG was also exploited as part of a rapid method for the identification of B. anthracis. We conclude that PlyG is a tool for the treatment and detection of B. anthracis.

A bacteriolytic agent that detects and kills Bacillus anthracis.

Properties and use of botulinum toxin and other microbial neurotoxins in medicine.

The action of botulinum toxin on the neuro‐muscular junction

The study of botulinum neurotoxins (BoNT) is rapidly progressing in many aspects. Novel BoNTs are being discovered owing to next generation sequencing, but their biologic and pharmacological properties remain largely unknown. The molecular structure of the large protein complexes that the toxin forms with accessory proteins, which are included in some BoNT type A1 and B1 pharmacological preparations, have been determined. By far the largest effort has been dedicated to the testing and validation of BoNTs as therapeutic agents in an ever increasing number of applications, including pain therapy. BoNT type A1 has been also exploited in a variety of cosmetic treatments, alone or in combination with other agents, and this specific market has reached the size of the one dedicated to the treatment of medical syndromes. The pharmacological properties and mode of action of BoNTs have shed light on general principles of neuronal transport and protein-protein interactions and are stimulating basic science studies. Moreover, the wide array of BoNTs discovered and to be discovered and the production of recombinant BoNTs endowed with specific properties suggest novel uses in therapeutics with increasing disease/symptom specifity. These recent developments are reviewed here to provide an updated picture of the biologic mechanism of action of BoNTs, of their increasing use in pharmacology and in cosmetics, and of their toxicology.

https://pharmrev.aspetjournals.org/content/pharmrev/69/2/200.full.pdf

Botulinum Neurotoxins: Biology, Pharmacology, and Toxicology.

SCIENCE: A Weekly Journal, since 1900 the official organ of the American Association for the Advancement of Science. Published by the American Association for the Advancement of Science every Friday at Lancaster, Pennsylvania. Communications relative to articles offered for publication should be addressed to Editor, Massachusetts and Nebraska Avenues, Washington 16, D. C. Inactivation of Penicillin by Zinc Salts: Hans Eisner and Bernardo Porzecanski ........................ A Note on Staining Plasmodia: A. W. Ratcliffe......... 629 630

https://science.sciencemag.org/content/sci/103/2681/613.full.pdf

The Purification and Crystallization of Clostridium botulinum Type A Toxin

Botulinum Toxin (Type A); Including a Study of Shaking with Chloroform as a Step in the Isolation Procedure.

The Isolation of Type B Botulinum Toxin.

The Taxonomy of the Genus Bacillus: I. Modes of Spore Germination.

Lamanna, Carl (Army Research Office, Washington, D.C.) and Linda Jones. Lethality for mice of vegetative and spore forms of Bacillus cereus and Bacillus cereus-like insect pathogens injected intraperitoneally and subcutaneously. J. Bacteriol. 85:532–535. 1963.—Lethality for mice of Bacillus thuringiensis var. thuringiensis (two strains), var. sotto (one strain), var. alesti (one strain), and B. entomocidus var. entomocidus (one strain) maintained on artificial laboratory media is dependent upon the route of injection, the number of the bacilli, and their biological state, i.e., vegetative or spore form. Deaths did not occur upon subcutaneous injection of tenfold greater numbers of organisms than the ld50 dose for the intraperitoneal route. From 10 to 100 times the number of spores were required to kill than vegetative bacilli given intraperitoneally. These observations duplicated those made with strains of B. cereus. For both types of spore forms, from 5 × 105 to 5 × 107 vegetative organisms were required for one intraperitoneal ld50. With two strains of highly virulent B. anthracis, ld50 values were the same for the vegetative and spore states, and for subcutaneous and intraperitoneal injections. Thus, the insect pathogenic sporeforming bacteria tested are more like B. cereus than like B. anthracis in their capacity to infect mice. The similarity to B. cereus extends to the rapidity of death after fatal injection of the insect pathogenic strains. The medical and taxonomic implications of the observations are discussed.

Lethality for mice of vegetative and spore forms of bacillus cereus and bacillus cereus-like insect pathogens injected intraperitoneally and subcutaneously

Carl Lamanna

Papers

The Purification and Crystallization of Clostridium botulinum Type A Toxin

Botulinum Toxin (Type A); Including a Study of Shaking with Chloroform as a Step in the Isolation Procedure.

The Isolation of Type B Botulinum Toxin.

The Taxonomy of the Genus Bacillus: I. Modes of Spore Germination.

Lethality for mice of vegetative and spore forms of bacillus cereus and bacillus cereus-like insect pathogens injected intraperitoneally and subcutaneously