Clostridium botulinum Neurotoxin: The Duality of a Microbe with Fatal and Therapeutic Applications

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Introduction

Magnified 20,000X, this colorized scanning electron micrograph (SEM) depicts a grouping of methicillin resistant Staphylococcus aureus (MRSA) bacteria. See PHIL 617 for a black and white view of this image. Phoro credit: CDC.

By Juliette Leclerc

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Clostridium botulinum is a gram-positive, rod-shaped, anaerobic, and spore-forming bacterium.[1] C. botulinum is made up of four different groups (I-IV), related by their collective ability to produce the neurotoxin botulinum.[2] Botulinum toxin has seven serotypes (A-G), most of which cause botulism, a neuroparalytic disease that can be fatal. There are several types of botulism, including food-borne, wound, infant, and iatrogenic botulism.[3] Clostridium botulinum is an extremely biologically diverse microorganism, and can exist in a variety of different environments and conditions, especially due its highly heat resistant spores, which create the botulinum toxin. Botulinum neurotoxin is the most potent natural toxin known to science, and despite even very small doses being fatal, it also has several therapeutic applications. Its most common application is in the cosmetics industry, as botulinum toxin is the active ingredient in Botox®.[4] Overall, Clostridium botulinum is a truly unique microbe that has an extraordinary range of applications in our world.



Sample citations: [5]

[6]

A citation code consists of a hyperlinked reference within "ref" begin and end codes.
To repeat the citation for other statements, the reference needs to have a names: "Cite error: Closing </ref> missing for <ref> tag Food-borne botulism, and therefore the Clostridium botulinum toxin, is thought to have accompanied humans since we first began storing and preserving food.[7] There are few sources available documenting cases of botulism prior to the 19th century, as the connection between food and death by paralysis had not yet been realized or established. The first to really delve into understanding food poisoning and food-borne botulism was Justinus Kerner (1786-1862), a medical officer in a small town in Germany.[7] During the Napoleonic wars, the sanitation of rural food production experienced a severe decline due to widespread poverty, which led to several documented outbreaks and cases of paralytic and fatal food poisoning, specifically relating to the consumption of blood sausage, a delicacy of the time.[8] Kerner ran numerous experiments on animals and himself to investigate the symptoms and onset of what he termed “sausage poison,” and eventually published the very first case study on botulism. He even suggested possible therapeutic applications of the toxin, which have since been proven to be a reality.The bacteria that produces the botulinum toxin was first isolated in 1895 by Emile Pierre-Marie van Ermengem following the death of 3 musicians at an event with a meal featuring smoked and pickled ham.[8] Ermengem, a microbiologist, performed autopsies on the bodies, as well as a detailed analysis of the ham itself. He originally named the bacterium Bacillus botulinum, inspired by the latin word for sausage, “botulus.” [7] Following its initial identification, a Dr. G. Landmann discovered in 1904 another bacterial toxin that caused botulism, this time isolated from a bean salad; the first of its kind to be found in a non-meat product. This bacterium was found to be distinct from the original toxin identified by Ermengem, which had been nonproteolytic, while this new one was in fact proteolytic.[9] This discovery marked the first identification of botulinum toxin serotypes, which we now know to be made up of types A-G, each immunologically distinct neurotoxins.[10] This new finding debuted a key notion: that different toxins may be produced by the same bacterial strains, just as the same toxin can be produced by different strains.[9] The proposal to change the genus name occurred in the 1920s, in order to separate the aerobic Bacillus species from the anaerobic Clostridium species, officially giving Clostridium botulinum its current name.[11]

Include some current research, with at least one figure showing data.

Propionibacterium acnes is a gram-positive, fairly slow-growing aerotolerant bacterium. This bacteria is typically linked to the skin condition acne vulgris, commonly known as skin acne. This species is daily commensal and highly present on healthy skin epithelium. Little is detected on the skin of adolescents, specifically those pre-pubescent. This bacterium lives on fatty acids in sebum secreted by hair sebaceous glands in hair follicles. It can also be found in the gastrointestinal biome.


Cell Biology

Include some current research, with at least one figure showing data.


Botulism disease

Include some current research, with at least one figure showing data.

Therapeutic Applications of Botulinum Toxin

Conclusion

References

  1. Johnson, E.A., Bradshaw, M., (2001) “Clostridium botulinum and its neurotoxins: a metabolic and cellular perspective,” Toxicon, 39(11), 1703-1722.
  2. [10.3389/fmicb.2016.01702 Brunt J., van Vliet A.H.M., van den Bos F., Carter A.T., Peck M.W. (2016) “Diversity of the Germination Apparatus in Clostridium botulinum Groups I, II, III, and IV,” Frontiers in Microbiology, 7.]
  3. Centers for Disease Control and Prevention. June 8, 2022. Botulism. U.S. Department of Health and Human Services.
  4. Nigam, P. K., & Nigam, A. (2010) “Botulinum toxin,” Indian journal of dermatology, 55(1), 8–14.
  5. Peck, M.W. (2009) “Biology and Genomic Analysis of Clostridium botulinum,” Advances in Microbial Physiology. Academic Press.Vol. 55, 183-320.
  6. Bartlett et al.: Oncolytic viruses as therapeutic cancer vaccines. Molecular Cancer 2013 12:103.
  7. 7.0 7.1 7.2 Erbguth, F.J. (2004) “Historical notes on botulism, Clostridium botulinum, botulinum toxin, and the idea of the therapeutic use of the toxin.” Mov. Disord., 19, S2-S6.
  8. 8.0 8.1 Cite error: Invalid <ref> tag; no text was provided for refs named Whitcup
  9. 9.0 9.1 Smith, T.J., Hill, K.K., Raphael, B.H. (2015) “Historical and current perspectives on Clostridium botulinum diversity,” Research in Microbiology, 166(4), 290-302.
  10. Oguma, K., Fujinaga, Y., Inoue, K., (1994) “Structure and Function of Clostridium botulinum Toxins,” Department of Bacteriology, Okayama University Medical School, 39(3), 161-168.
  11. Winslow, C. E., Broadhurst, J., Buchanan, R. E., Krumwiede, C., Rogers, L. A., & Smith, G. H. (1917). The Families and Genera of the Bacteria: Preliminary Report of the Committee of the Society of American Bacteriologists on Characterization and Classification of Bacterial Types. Journal of bacteriology, 2(5), 505–566.



Authored for BIOL 238 Microbiology, taught by Joan Slonczewski,at Kenyon College,2024