Category Archives: Molecule of the Moment

Botulinum Toxin

By Hannah Keane, Dec. 2016

What is it? What does it do?

Botulinum toxin (BTX) is a neurotoxic protein with 8 distinct serotypes [4]. All BTX exotoxins function as a polypeptide that blocks the release of a neurotransmitter, acetylcholine, involved in motor skills. BTX cleaves SNARE proteins preventing fusion of synaptic vesicles with the synaptic terminal; without fusion, acetylcholine cannot be released and muscle contractions are inhibited.

When was it discovered?

In 1897 botulism was first linked to the bacterial toxin by Emile Pierre van Ermengem, a bacteriologist at the University of Ghent in Belgium [3].

What produces it?

BTX is produced by Clostridium botulinum, a gram-positive anaerobic bacterium that commonly forms rod-shaped dormant spores [4].

Where is it found?

C. botulinum is pervasive in soil and marine environments, commonly found on plants, and also in mammalian intestinal tracts [4]. Botulism is most frequently caused by intoxication from ingesting food contaminated with the botulinum toxin [1].

Why is it important?

The risk of foodborne botulism in home-canned foods can be fatal. The recommendation for children less than 1-year-old to avoid consumption of honey is due to the presence of C. botulinum, which is known to cause infant botulism [1].

BTX is one of the most highly toxic biological compounds that currently exist, with potential as a bioterrorism agent.

Clinical uses range from cosmetic to medical applications in the treatment of wrinkles and strabismus, respectively. Therapeutic effects have been shown to improve a number of conditions [3].

Fun facts: Botox® was first produced in Irvine, California [4]. Botulism was named from the Latin word “botulus” which translates to sausage i.e. the source of intoxication [2].

 

illustration

illustration

 

Fig 1. Overview Botulinum toxin (Botox ®). (n.d.). Retrieved November 30, 2016, from http://www.oculoplastics.co.uk/botul_overview.php

References

[1] Botulism. (2016, May 03). Retrieved November 30, 2016, from Centers for Disease Control and Prevention, http://www.cdc.gov/botulism/

[2] Erbguth, Frank J. “Historical notes on botulism, Clostridium botulinum, botulinum toxin, and the idea of the therapeutic use of the toxin.” Movement Disorders 19.S8 (2004): S2-S6.

[3] Münchau, A., & Bhatia, K. P. (2000). Uses of botulinum toxin injection in medicine today. BMJ : British Medical Journal, 320(7228), 161–165.

[4] Nigam, P. K., & Nigam, A. (2010). BOTULINUM TOXIN. Indian Journal of Dermatology, 55(1), 8–14. http://doi.org/10.4103/0019-5154.60343

Mitomycin C

By Bushra Fatima, Dec. 2016

What is it?

Mitomycin C is a member of the mitomycin family of compounds, characterized by the presence of an aziridine ring. Mitomycin C was initially discovered as an antibiotic, but due to its antineoplastic properties has since been used in various cancer treatments. It is known to form covalent bonds with the DNA double helix, and these crosslinkages are the mechanism through which it causes cell death [1].

When was it discovered?

In late 1950s Dr Toju Hata and Dr. Shigetoshi Wakagi isolated mitomycin C from the fermentation broth of Streptomyces caespitosus [2].

Who produces it?

Mitomycin C is naturally produced by two Streptomyces species –Streptomyces caespitosus and Streptomyces lavendula, found in soil [3].

Where is it found?

It is present in the fermentation broth of Streptomyces species.

Why is it important?

Mitomycin C is a cytotoxic compound which, upon reduction, crosslinks the DNA double strands. This leads to inhibition of DNA synthesis, which in turn prevents cell proliferation. These antitumor properties of mitomycin C have led to its frequent use in treatment of various ocular tumors [4], along with other types of cancers. Mitomycin C is also used as an antibiotic agent due to its proficiency in killing bacteria through DNA crosslinkages [1].

Why was it chosen?

Mitomycin C has been shown to induce Streptococcus mitis prophage, SM1 [5].

Structure:

m1

Fig 1. Mitomycin C structure from Wikipedia

m2

Fig. 2. Mechanism of DNA cross-linking from Tomasz, Maria. “Mitomycin C: Small, Fast and Deadly (but Very Selective).” Chemistry & Biology 2.9 (1995): 575-79.

 

References

[1] Tomasz, Maria. “Mitomycin C: Small, Fast and Deadly (but Very Selective).” Chemistry & Biology 2.9 (1995): 575-79. Web.

[2] Nemade, Hemant, Hussein Tukmatchy, and Peter Thompson. “Fri-10 Mitomycin-C: Historical Aspects Of The Discovery Of Most Commonly Used Chemotherapy Agent In Urology.” The Journal of Urology 193.4 (2015): n. pag. Web

[3] Danshiitsoodol, Narandalai, Catherine Azzariti De Pinho, Yasuyuki Matoba, Takanori Kumagai, and Masanori Sugiyama. “The Mitomycin C (MMC)-binding Protein from MMC-producing Microorganisms Protects from the Lethal Effect of Bleomycin: Crystallographic Analysis to Elucidate the Binding Mode of the Antibiotic to the Protein.” Journal of Molecular Biology 360.2 (2006): 398-408. Web.

[4] Mearza, Ali A., and Ioannis M. Aslanides. “Uses and Complications of Mitomycin C in Ophthalmology.” Expert Opinion on Drug Safety 6.1 (2006): 27-32. Web.

[5] Willner, Dana et al. “Metagenomic Detection of Phage-Encoded Platelet-Binding Factors in the Human Oral Cavity.” Proceedings of the National Academy of Sciences of the United States of America 108.Suppl 1 (2011): 4547–4553. PMC. Web. 30 Nov. 2016.

Streptococcus salivarius

By Sanika Joshi, Dec 2016

What is it?

Streptococcus salivarius is a gram-positive, facultative anaerobic microorganism that is found in the oral cavity and upper respiratory tract of human beings. S. salivarius is spherical in shape, non-motile, non-sporing, and catalase negative. Although it is a common member of the oral microflora in healthy individuals, S. salivarius is an opportunistic pathogen capable of infecting immunocompromised patients [1].

When was it discovered?

The first description of streptococcal infection was made by Austrian surgeon Theodor Billroth in 1874. Then in 1879, Louis Pasteur isolated Streptococcus from the uterus and blood from women with post-labor uterine infections known as puerperal fever [2].

Where is it found?

S. salivarius is one of the earliest bacteria that colonizes the dental plaques of newborns [3]. S. salivarius is a primary colonizer of teeth, acting as a substrate for the attachment of other oral microbes. Oral microbiota form “hedgehog” structures in dental plaques, in which Streptococcus species make up the structure’s base and tip [4]. S. salivarius remains prevalent as a commensal in the human oropharyngeal tract throughout healthy individuals’ lives [3]. Streptococcus species also colonize the lungs of cystic fibrosis patients [5].

Why is it important?

S. salivarius K12 was the first strain to be commercially developed as an oral probiotic and it helps to improve oral health and reduces halitosis, or bad breath [6]. In rare cases, S. salivarius can enter the blood stream and cause septicemia (systemic bacterial infection) or endocarditis (heart disease) [2].

fish

Fig 1. Streptococci make up the base and distal ends of “hedgehog” structures found on dental plaques. Streptococcus species were stained green and Corynebacterium were stained magenta using FISH probes. Size of scale bar = 20 microns. Figure obtained from: Welch JL, et al. 2016. Biogeography of a human oral microbiome at the micron scale. PNAS, 113(6): E791-800.

References

[1] Kaci G, et al. 2014. Anti-Inflammatory Properties of Streptococcus salivarius, a Commensal Bacterium of the Oral Cavity and Digestive Tract. Applied and Environmental Microbiology, 80(3): 928–934. http://doi.org/10.1128/AEM.03133-13

[2] Ferretti J, et al. 2016. Streptococcus pyogenes : Basic Biology to Clinical Manifestations [Internet]. Oklahoma City (OK): University of Oklahoma Health Sciences Center; 2016-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK333430/

[3] Streptococcus salivarius. 12 April 2011. https://microbewiki.kenyon.edu/index.php/Streptococcus_salivarius

[4] Welch JL, et al. 2016. Biogeography of a human oral microbiome at the micron scale. PNAS, 113(6): E791-800.

[5] Lim YW, et al. 2014. Clinical Insights from Metagenomic Analysis of Sputum Samples from Patients with Cystic Fibrosis. Journal of Clinical Microbiology, 52(2): 425-437.

[6] Burton JP, et al. 2006. A preliminary study of the effect of probiotic Streptococcus salivarius K12 on oral malodour parameters. Journal of applied microbiology, 100(4): 754-764.

Pyocyanin

PYOCYANIN            

By: Joann Phan, with commentary from the September 26th Whiteson lab meeting

What is it? Pyocyanin is a redox active molecule, a phenazine, that is often produced by soil microbes. Phenazines have long been considered as antibiotics used as weapons in microbial community interactions. However, in low oxygen conditions, they can act as an alternative electron acceptor, expanding the ability of a bacteria to respire without much oxygen [1]. In the presence of oxygen, pyocyanin can be distinguished by its vibrant blue color.

When was it discovered? In the early 19th century in tainted “blue milk” [2].  In 1859, Mathurin-Joseph Fordos isolated this blue pigment from pus infected wounds [3].

Who produces it? Several Gram-negative bacteria, including Pseudomonas aeruginosa, are known to produce phenazines, including pyocyanin.

Where is it found? In many different environments, where some Gram-negative bacteria grow, including soil and chronic human infections such as wounds or the airways of Cystic Fibrosis (CF) patients [4].

Why is it important? Pyocyanin is both an alternative electron acceptor in low oxygen conditions, and it is capable of producing toxic redox molecules in the presence of oxygen, which can destroy neighboring microbial or even mammalian cells. In the sputum of CF patients, there is more pyocyanin found in patients as their lung function declines [4].

Image:                                                       Structure:

Left, Pseudomonas aeruginosa culture in presence of oxygen, taken by Joann Phan

Right, Pyocyanin structure from Wikipedia

References:

[1] Glasser, N. R., Kern, S., E. and Dianne K. Newman. (2014) Phenazine redox cycling enhances anaerobic survival in Pseudomonas aeruginosa by facilitating generation of ATP and a proton-motive force. Molecular Microbiology 92(2): 399-412.

[2] Jordan EO. (1899) BACILLUS PYOCYANEUS AND ITS PIGMENTS. The Journal of Experimental Medicine. 4(5-6):627-647.

[3]  Fordos, Mathurin-Joseph – Dictionary definition of Fordos, Mathurin-Joseph | Encyclopedia.com. Retrieved from http://www.encyclopedia.com/doc/1G2-2830901476.html

[4] Hunter, R. C., Kepac-Ceraj, V., Lorenzi, M. M., Grotzinger, H., Martin, T. R., and Dianne K. Newman. (2012) Phenazine content in the Cystic Fibrosis respiratory tract negatively correlates with lung function and microbial complexity. American Journal of Respiratory Cell and Molecular Biology. 47(6): 738-745.

M.O.M. List

Here are some options for Molecule/Microbe of the moment.

Completed molecules (or microbes) are linked.

  • Butanedione
  • crAssphage
  • Enterococcus faecium
  • Leuconostoc Mesenteroides
  • Lactobacillus Rhamnosus
  • MPP, Mysterious Purple Pigment
  • Pseudomonas syringae
  • Putriscine
  • Pyocyanin
  • Yersinia pestis