Clostridium sporogenes

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Clostridium sporogenes
Clostridium botulinum 01.png
Clostridium botulinum stained with gentian violet.
Scientific classification
Domain: Bacteria
Class: Clostridia
Order: Clostridiales
Family: Clostridiaceae
Genus: Clostridium
Species: C. sporogenes
Binomial name
Clostridium sporogenes
(Metchnikoff 1908) Bergey et al. 1923[1]

Clostridium sporogenes is a species of Gram-positive bacteria that belongs to the genus Clostridium. Like other strains of Clostridium, it is an anaerobic, rod-shaped bacterium that produces oval, subterminal endospores and is commonly found in soil. Unlike Clostridium botulinum, it does not produce the botulinum neurotoxins. In colonized animals, it has a mutualistic rather than pathogenic interaction with the host.

It is being investigated as a way to deliver cancer-treating drugs to tumours in patients.[2] C. sporogenes is often used as a surrogate for C. botulinum when testing the efficacy of commercial sterilisation.[3]

C. sporogenes colonizes the human gastrointestinal tract, but is only present in a subset of the population; in the intestine, it uses tryptophan to synthesize indole and subsequently 3-indolepropionic acid (IPA)[4] – a type of auxin (plant hormone)[5][6] – which serves as a potent antioxidant within the human body and brain.[4][7][8] IPA is an even more potent scavenger of hydroxyl radicals than melatonin.[7][8] Similar to melatonin but unlike other antioxidants, it scavenges radicals without subsequently generating reactive and pro-oxidant intermediate compounds.[7][8][9] C. sporogenes is the only bacteria known to synthesize 3-indolepropionic acid in vivo at levels which are subsequently detectable in the blood stream of the host.[4][10]

Tryptophan metabolism by human gastrointestinal microbiota (v · t · e)
Tryptophan metabolism diagram
This diagram shows the biosynthesis of bioactive compounds (indole and certain derivatives) from tryptophan by bacteria in the gut.[11] Indole is produced from tryptophan by bacteria that express tryptophanase.[11] Clostridium sporogenes metabolizes indole into 3-indolepropionic acid (IPA),[4] a highly potent neuroprotective antioxidant that scavenges hydroxyl radicals.[11][7][8] In the intestine, IPA binds to pregnane X receptors (PXR) in intestinal cells, thereby facilitating mucosal homeostasis and barrier function.[11] Following absorption from the intestine and distribution to the brain, IPA confers a neuroprotective effect against cerebral ischemia and Alzheimer’s disease.[11] Lactobacillus species metabolize tryptophan into indole-3-aldehyde (I3A) which acts on the aryl hydrocarbon receptor (AhR) in intestinal immune cells, in turn increasing interleukin-22 (IL-22) production.[11] Indole itself acts as a glucagon-like peptide-1 (GLP-1) secretagogue in intestinal L cells and as a ligand for AhR.[11] Indole can also be metabolized by the liver into indoxyl sulfate, a compound that is toxic in high concentrations and associated with vascular disease and renal dysfunction.[11] AST-120 (activated charcoal), an intestinal sorbent that is taken by mouth, adsorbs indole, in turn decreasing the concentration of indoxyl sulfate in blood plasma.[11]

References[edit]

  1. ^ "Clostridium sporogenes". US Department of Energy. Retrieved 5 September 2011. 
  2. ^ BBC News "Soil bacterium helps kill cancers."
  3. ^ Development of novel biological indicators to evaluate the efficacy of microwave processing. Proquest. p. 7. 
  4. ^ a b c d Wikoff WR, Anfora AT, Liu J, Schultz PG, Lesley SA, Peters EC, Siuzdak G (2009). "Metabolomics analysis reveals large effects of gut microflora on mammalian blood metabolites". Proc. Natl. Acad. Sci. U.S.A. 106 (10): 3698–703. doi:10.1073/pnas.0812874106. PMC 2656143. PMID 19234110. Production of IPA was shown to be completely dependent on the presence of gut microflora and could be established by colonization with the bacterium Clostridium sporogenes. 
    IPA metabolism diagram
  5. ^ Lu Q, Zhang L, Chen T, Lu M, Ping T, Chen G (2008). "Identification and quantitation of auxins in plants by liquid chromatography/electrospray ionization ion trap mass spectrometry". Rapid Commun. Mass Spectrom. 22 (16): 2565–72. doi:10.1002/rcm.3642. PMID 18655000. 
  6. ^ Narayanan KR, Mudge KW, Poovaiah BW (1981). "In vitro auxin binding to cellular membranes of cucumber fruits". Plant Physiol. 67 (4): 836–40. doi:10.1104/pp.67.4.836. PMC 425782. PMID 16661764. 
  7. ^ a b c d "3-Indolepropionic acid". Human Metabolome Database. University of Alberta. Retrieved 12 October 2015. Indole-3-propionate (IPA), a deamination product of tryptophan formed by symbiotic bacteria in the gastrointestinal tract of mammals and birds. 3-Indolepropionic acid has been shown to prevent oxidative stress and death of primary neurons and neuroblastoma cells exposed to the amyloid beta-protein in the form of amyloid fibrils, one of the most prominent neuropathologic features of Alzheimer's disease. 3-Indolepropionic acid also shows a strong level of neuroprotection in two other paradigms of oxidative stress. (PMID 10419516 )
    Origin:  • Endogenous  • Microbial
     
  8. ^ a b c d Chyan YJ, Poeggeler B, Omar RA, Chain DG, Frangione B, Ghiso J, Pappolla MA (1999). "Potent neuroprotective properties against the Alzheimer beta-amyloid by an endogenous melatonin-related indole structure, indole-3-propionic acid". J. Biol. Chem. 274 (31): 21937–42. doi:10.1074/jbc.274.31.21937. PMID 10419516. [Indole-3-propionic acid (IPA)] has previously been identified in the plasma and cerebrospinal fluid of humans, but its functions are not known. ... In kinetic competition experiments using free radical-trapping agents, the capacity of IPA to scavenge hydroxyl radicals exceeded that of melatonin, an indoleamine considered to be the most potent naturally occurring scavenger of free radicals. In contrast with other antioxidants, IPA was not converted to reactive intermediates with pro-oxidant activity. 
  9. ^ Reiter RJ, Guerrero JM, Garcia JJ, Acuña-Castroviejo D (1998). "Reactive oxygen intermediates, molecular damage, and aging. Relation to melatonin". Ann. N. Y. Acad. Sci. 854: 410–24. doi:10.1111/j.1749-6632.1998.tb09920.x. PMID 9928448. 
  10. ^ Attwood G, Li D, Pacheco D, Tavendale M (2006). "Production of indolic compounds by rumen bacteria isolated from grazing ruminants". J. Appl. Microbiol. 100 (6): 1261–71. doi:10.1111/j.1365-2672.2006.02896.x. PMID 16696673. 
  11. ^ a b c d e f g h i Zhang LS, Davies SS (April 2016). "Microbial metabolism of dietary components to bioactive metabolites: opportunities for new therapeutic interventions". Genome Med 8 (1): 46. doi:10.1186/s13073-016-0296-x. PMC 4840492. PMID 27102537. Lactobacillus spp. convert tryptophan to indole-3-aldehyde (I3A) through unidentified enzymes [125]. Clostridium sporogenes convert tryptophan to IPA [6], likely via a tryptophan deaminase. ... IPA also potently scavenges hydroxyl radicals 
    Table 2: Microbial metabolites: their synthesis, mechanisms of action, and effects on health and disease
    Figure 1: Molecular mechanisms of action of indole and its metabolites on host physiology and disease

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