Microbial toxin

Microbial toxins are toxins produced by micro-organisms, including bacteria, fungi, protozoa, dinoflagellates, and viruses. Many microbial toxins promote infection and disease by directly damaging host tissues and by disabling the immune system. The botulinum toxin, which is primarily produced by Clostridium botulinum and less frequently by other Clostridium species, is the most toxic substance known in the world.[1] However, microbial toxins also have important uses in medical science and research. Currently, new methods of detecting bacterial toxins are being developed to better isolate and understand these toxin. Potential applications of toxin research include combating microbial virulence, the development of novel anticancer drugs and other medicines, and the use of toxins as tools in neurobiology and cellular biology.[2]

Bacterial toxin

Bacteria generate toxins which can be classified as either exotoxins or endotoxins. Exotoxins are generated and actively secreted; endotoxins remain part of the bacteria. Usually, an endotoxin is part of the bacterial outer membrane, and it is not released until the bacterium is killed by the immune system. The body's response to an endotoxin can involve severe inflammation. In general, the inflammation process is usually considered beneficial to the infected host, but if the reaction is severe enough, it can lead to sepsis.

Some bacterial toxins can be used in the treatment of tumors.[3]

Toxinosis is pathogenesis caused by the bacterial toxin alone, not necessarily involving bacterial infection (e.g. when the bacteria have died, but have already produced toxin, which are ingested). It can be caused by Staphylococcus aureus toxins, for example.[4]

Examples

Clostridial toxins

There are over 200 Clostridium species in the world that live in mundane places such as soil, water, dust, and even our digestive tracts. Some of these species produce harmful toxins such as botulinum toxin and tetanus toxin among others. Most clostridium species that do have toxins typically have binary toxins with the first unit involved in getting the toxin into the cell and the second unit cause cellular stress or deformation.[5]

Botulinum neurotoxin

Botulinum neurotoxins (BoNTs) are the causative agents of the deadly food poisoning disease botulism, and could pose a major biological warfare threat due to their extreme toxicity and ease of production. They also serve as powerful tools to treat an ever expanding list of medical conditions.[6]

Tetanus toxin

Clostridium tetani produces tetanus toxin (TeNT protein), which leads to a fatal condition known as tetanus in many vertebrates (including humans) and invertebrates.

Staphylococcal toxins

Immune evasion proteins from Staphylococcus aureus have a significant conservation of protein structures and a range of activities that are all directed at the two key elements of host immunity, complement and neutrophils. These secreted virulence factors assist the bacterium in surviving immune response mechanisms.[7]

Detection methods in fresh water environments

Cyanobacteria are an important autotrophic bacteria in the water food web. Explosions of cyanobacteria known as algal blooms can produce toxins harmful to both the ecosystem and human health. Detection of the extent of an algal bloom begins by taking samples of water at various depths and locations in the bloom.[8]

Solid-phase adsorption toxin tracking (SPATT)

SPATT is a useful tool in tracking algal blooms as it is reliable, sensitive, and inexpensive. One of the downsides is that it does not give very good results for water soluble toxins as compared to hydrophobic compounds. This tool is mainly used to determine intercellular concentrations of toxins but the cyanobacteria can also be lysed to determine the total toxin amount in a sample.[8]

Polymerase chain reaction (PCR)

PCR is a molecular tool that allows for analysis of genetic information. PCR is used to amplify the amount of certain DNA within a sample which are usually specific genes within a sample. Genetic targets for cyanobacteria in PCR include the 16S ribosomal RNA gene, phycocyanin operon, internal transcribed spacer region, and the RNA polymerase β subunit gene. PCR is effective when the gene of a known enzyme for producing the microbial toxin or the microbial toxin itself is known.[8]

Enzyme inhibition

There are many diverse ways of monitoring enzyme levels through the use of enzyme inhibition. The general principle in many of these is the use the knowledge that many enzymes are driven by phosphate-releasing compounds such as adenosine triphosphate. Using radiolabelled 32P phosphate a fluorometric analysis can be used. Or unique polymers can be used to immobilize enzymes and act in an electrochemical biosensor. Overall, the benefits include a fast response time and little sample preparation. Some of the downsides include a lack of specificity in terms of being able to get readings of very small amounts of toxin and the rigidity of the assays in apply certain procedures to different toxins.[8]

Immunochemical methods

This detection method uses mammalian antibodies to bind to microbial toxins which can then be processed in a variety of different ways. Of the commercial ways of using immunochemical detection would be enzyme-linked immunosorbent assays (ELISA). This assay has the advantage of being able to screen for a broad range of toxins but could have issues with specificity depending on the antibody used.[8] A more exotic setup involves the use of CdS quantum dots which are used in an electro-chemiluminescent immunosensor.[9] A major aspect of immunochemical methods being tested in laboratories are uses of nanowires and other nanomaterials to detect microbial toxins.[8]

Tetrodotoxins

These toxins are produced by vibrio species of bacteria and like to accumulate in marine life such as the pufferfish. These toxins are produced when vibrio bacteria are stressed by changes in temperature and salinity of environment which leads towards production of toxins. The main hazard towards humans is during consumption of contaminated seafood. Tetrodotoxin poisoning is becoming common in more northern and typically colder marine waters as higher precipitation and warmer waters from climate change triggers vibrio bacteria to produce toxins. [10]

Viral toxin

There is only one viral toxin that has been described so far: NSP4 from rotavirus. It inhibits the microtubule-mediated secretory pathway and alters cytoskeleton organization in polarized epithelial cells. It has been identified as the viral enterotoxin based on the observation that the protein caused diarrhea when administered intraperitoneally or intra-ileally in infant mice in an age-dependent manner.[11] NSP4 can induce aqueous secretion in the gastrointestinal tract of neonatal mice through activation of an age- and Ca2+-dependent plasma membrane anion permeability.[12]

See also

References

  1. ↑ K R Kessler & R Benecke (1997). "Botulinum toxin: from poison to remedy - PubMed". Neurotoxicology. Retrieved 27 December 2021. Botulinum toxins, exotoxins of Clostridium botulinum, are the most toxic naturally occurring substances known to man.
  2. ↑ Microbial toxins : current research and future trends. Proft, Thomas. Norfolk: Caister Academic Press. 2009. ISBN 978-1-904455-44-8. OCLC 280543853.{{cite book}}: CS1 maint: others (link)
  3. ↑ "NCI Dictionary of Cancer Terms". National Cancer Institute. 2011-02-02. Retrieved 2020-05-05.
  4. ↑ Harvey RA, Champe PC, Fisher BD (2007). Microbiology (2nd ed.). Philadelphia: Lippincott Williams & Wilkins. ISBN 978-0-7817-8215-9. OCLC 67817144.
  5. ↑ Knapp O, Benz R, Popoff MR (March 2016). "Pore-forming activity of clostridial binary toxins". Biochimica et Biophysica Acta (BBA) - Biomembranes. Pore-Forming Toxins: Cellular Effects and Biotech Applications. 1858 (3): 512–25. doi:10.1016/j.bbamem.2015.08.006. PMID 26278641.
  6. ↑ Microbial toxins : current research and future trends. Proft, Thomas. Norfolk: Caister Academic Press. 2009. ISBN 978-1-904455-44-8. OCLC 280543853.{{cite book}}: CS1 maint: others (link)
  7. ↑ Microbial toxins : current research and future trends. Proft, Thomas. Norfolk: Caister Academic Press. 2009. ISBN 978-1-904455-44-8. OCLC 280543853.{{cite book}}: CS1 maint: others (link)
  8. 1 2 3 4 5 6 Picardo M, Filatova D, Nuñez O, Farré M (2019-03-01). "Recent advances in the detection of natural toxins in freshwater environments". TrAC Trends in Analytical Chemistry. 112: 75–86. doi:10.1016/j.trac.2018.12.017.
  9. ↑ Zhang J, Kang T, Hao Y, Lu L, Cheng S (2015-07-31). "Electrochemiluminescent immunosensor based on CdS quantum dots for ultrasensitive detection of microcystin-LR". Sensors and Actuators B: Chemical. 214: 117–123. doi:10.1016/j.snb.2015.03.019. ISSN 0925-4005.
  10. ↑ Clark GC, Casewell NR, Elliott CT, Harvey AL, Jamieson AG, Strong PN, Turner AD (April 2019). "Friends or Foes? Emerging Impacts of Biological Toxins". Trends in Biochemical Sciences. 44 (4): 365–379. doi:10.1016/j.tibs.2018.12.004. PMID 30651181.
  11. ↑ Jagannath MR, Kesavulu MM, Deepa R, Sastri PN, Kumar SS, Suguna K, Rao CD (January 2006). "N- and C-terminal cooperation in rotavirus enterotoxin: novel mechanism of modulation of the properties of a multifunctional protein by a structurally and functionally overlapping conformational domain". Journal of Virology. 80 (1): 412–25. doi:10.1128/JVI.80.1.412-425.2006. PMC 1317517. PMID 16352566.
  12. ↑ Borghan MA, Mori Y, El-Mahmoudy AB, Ito N, Sugiyama M, Takewaki T, Minamoto N (July 2007). "Induction of nitric oxide synthase by rotavirus enterotoxin NSP4: implication for rotavirus pathogenicity". The Journal of General Virology. 88 (Pt 7): 2064–72. doi:10.1099/vir.0.82618-0. PMID 17554041.
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