Clostridium sporogenes

Clostridium sporogenes
Scientific classification
Domain: Bacteria
Kingdom: Bacillati
Phylum: Bacillota
Class: Clostridia
Order: Eubacteriales
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[2] and is commonly found in soil.

C. sporogenes is being investigated as a way to deliver cancer-treating drugs to tumours in patients.[3][4] C. sporogenes is often used as a surrogate for C. botulinum when testing the efficacy of commercial sterilisation.[5][6]

Metabolism

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)[7] – a type of auxin (plant hormone)[8][9] – which serves as a potent neuroprotective antioxidant within the human body and brain.[7][10][11][12] IPA is an even more potent scavenger of hydroxyl radicals than melatonin.[10][11][12] Similar to melatonin but unlike other antioxidants, it scavenges radicals without subsequently generating reactive and pro-oxidant intermediate compounds.[10][11][13] C. sporogenes is the only species of bacteria known to synthesize 3-indolepropionic acid in vivo at levels which are subsequently detectable in the blood stream of the host.[7][14]

Tryptophan metabolism by human gut microbiota ()
This diagram shows the biosynthesis of bioactive compounds (indole and certain other derivatives) from tryptophan by bacteria in the gut.[12] Indole is produced from tryptophan by bacteria that express tryptophanase.[12] Clostridium sporogenes metabolizes tryptophan into indole and subsequently 3-indolepropionic acid (IPA),[7] a highly potent neuroprotective antioxidant that scavenges hydroxyl radicals.[12][10][11] IPA binds to the pregnane X receptor (PXR) in intestinal cells, thereby facilitating mucosal homeostasis and barrier function.[12] Following absorption from the intestine and distribution to the brain, IPA confers a neuroprotective effect against cerebral ischemia and Alzheimer's disease.[12] Lactobacillaceae (Lactobacillus s.l.) 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.[12] Indole itself triggers the secretion of glucagon-like peptide-1 (GLP-1) in intestinal L cells and acts as a ligand for AhR.[12] 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.[12] 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.[12]

Older literature has also reported production of thiaminase I by some strains of C. sporogenes, an enzyme capable of degrading thiamine.[15][16][17] Early studies implicated thiamine deficiency in the development of polioencephalomalacia (also known as cerebrocortical necrosis) in ruminants.[18][19][20] However, the role of bacterial thiaminases in the development of polioencephalomalacia in ruminants remains debated.[21]

Clinical significance

C. sporogenes is generally regarded as a non-pathogenic anaerobe. However, rare cases of opportunistic infections have been reported in humans, including cases of bacteremia, soft tissue infection, septic arthritis, and clostridial myonecrosis.[22][23][24][25][26][27][28][29][30][31] Similar infections have also been described in domestic animals.[32][33][34][35]

Genomic and phylogenetic studies indicate that C. sporogenes is closely related to toxigenic group I clostridia (including C. botulinum)[36] and that some strains possess the capability to produce botulism neurotoxins (BoNTs), predominantly BoNT/B serotypes.[37][38][39] A palaeogenomic study of cattle remains from a Roman-era mass grave identified a Clostridium strain phylogenetically positioned between C. sporogenes and group I C. botulinum and concluded it may represent an ancient C. sporogenes lineage which carried several virulence-associated genes, suggesting that some historical strains may have already displayed pathogenic potential.[40]

References

  1. ^ Parker, Charles Thomas; Taylor, Dorothea; Garrity, George M. (2009). Parker, Charles Thomas; Garrity, George M (eds.). "Clostridium sporogenes". US Department of Energy. doi:10.1601/nm.4021. Retrieved 5 September 2011. {{cite journal}}: Cite journal requires |journal= (help)
  2. ^ Janganan, Thamarai K.; Mullin, Nic; Dafis-Sagarmendi, Ainhoa; Brunt, Jason; Tzokov, Svetomir B.; Stringer, Sandra; Moir, Anne; Chaudhuri, Roy R.; Fagan, Robert P.; Hobbs, Jamie K.; Bullough, Per A. (2020-07-01). "Architecture and Self-Assembly of Clostridium sporogenes and Clostridium botulinum Spore Surfaces Illustrate a General Protective Strategy across Spore Formers". mSphere. 5 (4): e00424–20. doi:10.1128/mSphere.00424-20. ISSN 2379-5042. PMC 7333573. PMID 32611700.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  3. ^ Heap, John T.; Theys, Jan; Ehsaan, Muhammad; Kubiak, Aleksandra M; Dubois, Ludwig; Paesmans, Kim; Van Mellaert, Lieve; Knox, Richard; Kuehne, Sarah A.; Lambin, Phillipe; Minton, Nigel P. (2014-04-15). "Spores of Clostridium engineered for clinical efficacy and safety cause regression and cure of tumors in vivo". Oncotarget. 5 (7): 1761–1769. doi:10.18632/oncotarget.1761. ISSN 1949-2553. PMC 4039107. PMID 24732092.
  4. ^ Singh, Saloni; Kim, Geun-Hyung; Baek, Kwang-Rim; Seo, Seung-Oh (2025-03-14). "Anti-Cancer Strategies Using Anaerobic Spore-Forming Bacteria Clostridium: Advances and Synergistic Approaches". Life. 15 (3): 465. doi:10.3390/life15030465. ISSN 2075-1729. PMC 11943571. PMID 40141809.
  5. ^ Development of novel biological indicators to evaluate the efficacy of microwave processing. p. 7. ISBN 978-0-549-83045-0.
  6. ^ Koukou, Ioulia; Stergioti, Thomai; la Cour, Rasmus; Gkogka, Elissavet; Dalgaard, Paw (1 October 2022). "Clostridium sporogenes as surrogate for proteolytic C. botulinum - Development and validation of extensive growth and growth-boundary model". Food Microbiology. 107 104060. doi:10.1016/j.fm.2022.104060. ISSN 0740-0020.
  7. ^ a b c d Wikoff WR, Anfora AT, Liu J, Schultz PG, Lesley SA, Peters EC, Siuzdak G (March 2009). "Metabolomics analysis reveals large effects of gut microflora on mammalian blood metabolites". Proc. Natl. Acad. Sci. U.S.A. 106 (10): 3698–3703. Bibcode:2009PNAS..106.3698W. 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
  8. ^ 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. Bibcode:2008RCMS...22.2565L. doi:10.1002/rcm.3642. PMID 18655000.
  9. ^ 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.
  10. ^ a b c d "3-Indolepropionic acid". Human Metabolome Database. University of Alberta. Retrieved 12 June 2018.
  11. ^ a b c d Chyan YJ, Poeggeler B, Omar RA, Chain DG, Frangione B, Ghiso J, Pappolla MA (July 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): 21937–21942. doi:10.1074/jbc.274.31.21937. PMID 10419516. S2CID 6630247. [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.
  12. ^ a b c d e f g h i j k 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
  13. ^ 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 (1): 410–24. Bibcode:1998NYASA.854..410R. doi:10.1111/j.1749-6632.1998.tb09920.x. PMID 9928448. S2CID 29333394.
  14. ^ 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. S2CID 35673610.
  15. ^ Hayashi, Ryoji; Yoshii, Zensaku; Harada, Tomoyasu; Nigota, Kimitoshi; Tsubota, Yoko; Shibutake, Machiko; Sasaki, Masato; Suzuki, Shoichiro; Takagi, Testuro (1964). "STUDIES ON THIAMINASE OF THE CLOSTRIDIUM". THE JOURNAL OF VITAMINOLOGY. 10 (2): 168–171. doi:10.5925/jnsv1954.10.168. ISSN 0022-5398.
  16. ^ Hayashi, Ryoji; Yoshii, Zensaku; Kobayashi, Susumu; Kawaguchi, Nobuyuki (1973). "Thiaminase Activities of Clostridium sporogenes and Cl. botulinum". Proceedings of the Japan Academy. 49 (1): 37–41. doi:10.2183/pjab1945.49.37.
  17. ^ Princewill, T.J.T. (April 1980). "Thiaminase Activity Amongst Strains of Clostridium sporogenes". Journal of Applied Bacteriology. 48 (2): 249–252. doi:10.1111/j.1365-2672.1980.tb01223.x. ISSN 0021-8847.
  18. ^ Edwin, E. E.; Jackman, Roy (November 1970). "Thiaminase I in the Development of Cerebrocortical Necrosis in Sheep and Cattle". Nature. 228 (5273): 772–774. doi:10.1038/228772a0. ISSN 0028-0836.
  19. ^ Edwin, E.E.; Markson, L.M.; Jackman, R. (July 1982). "The Aetiology of Cerebrocortical Necrosis: The Role of Thiamine Deficiency and of Deltapyrrolinium". British Veterinary Journal. 138 (4): 337–349. doi:10.1016/S0007-1935(17)31039-4.
  20. ^ Thornber, E. J.; Dunlop, R. H.; Gawthorne, J. M.; Huxtable, C. R. (May 1979). "Polioencephalomalacia (cerebrocortical necrosis) induced by experimental thiamine deficiency in lambs". Research in Veterinary Science. 26 (3): 378–380. ISSN 0034-5288. PMID 515526.
  21. ^ Boyd, J. W.; Walton, J. R. (1977-10-01). "Cerebrocortical necrosis in ruminants: An attempt to identify the source of thiaminase in affected animals". Journal of Comparative Pathology. 87 (4): 581–589. doi:10.1016/0021-9975(77)90064-0. ISSN 0021-9975.
  22. ^ Abusnina, Waiel; Shehata, Mena; Karem, Emhemmid; Koc, Zeynep; Khalil, Elie (1 January 2019). "Clostridium sporogenes bacteremia in an immunocompetent patient". IDCases. 15 e00481. doi:10.1016/j.idcr.2018.e00481. ISSN 2214-2509.
  23. ^ Harith A, Alataby; Vaishali, Krishnamoorthy; Laura, Ndzelen; Foma Munoh, Kenne; Kate, Valenti; Jessie, Savermuttu; Jay, Nfonoyim (2020-01-15). "Clostridium Sporogenes Causing Bacteremia Originated from the Skin and Soft Tissue Infection in an Immunocompetent Patient - Case Report and Literature Review". International Journal of Critical Care and Emergency Medicine. 6 (1). doi:10.23937/2474-3674/1510095.
  24. ^ Cobo, Fernando; Pérez-Carrasco, Virginia; García-Salcedo, José A.; Navarro-Marí, José María (2023-03-10). "Bacteremia caused by Clostridium sporogenes in an oncological patient". Revista Española de Quimioterapia. 36 (2): 217–219. doi:10.37201/req/111.2022. PMC 10066920. PMID 36698324.
  25. ^ Chaudhary, Preeti; Gulati, Neelam; Gupta, Varsha; Dhanda, Gazal; Kumar, Mani Bhushan; Sharma, Swati; Goel, Anku; Kumar Attri, Ashok (May 2023). "Fatal Clostridium sporogenes Soft Tissue Polymicrobial Infections in Two Immunocompetent Cases: Case Report". Infectious Disorders - Drug Targets. 23 (3). doi:10.2174/1871526523666230112161134.
  26. ^ Kanaujia, Rimjhim; Dahiya, Divya; Banda, Ashwin Rao; Ray, Pallab; Angrup, Archana (June 2020). "Non-traumatic gas gangrene due to Clostridium sporogenes". The Lancet Infectious Diseases. 20 (6): 754. doi:10.1016/S1473-3099(20)30024-4.
  27. ^ Truong, Rachel D.; Do, Van Anh; Njaravelil, Kristi A.; Ayesu, Kwabena; Madruga, Mario; Carlan, Steve J. (2023-10-17). "Ludwig Angina Caused by Clostridium sporogenes in a 49-Year-Old HIV-Positive Man with Alcoholism and a Tooth Abscess: The First Reported Case". American Journal of Case Reports. 24. doi:10.12659/AJCR.941731. ISSN 1941-5923.
  28. ^ Shen, Ding-Xia; Babady, N. Esther; Chen, Rong; Gilhuley, Kathleen; Tang, Yi-Wei (July 2013). "Septicaemia caused by Clostridium sporogenes: two case reports and a literature review". Reviews in Medical Microbiology. 24 (3): 81–83. doi:10.1097/MRM.0b013e328362fa5b. ISSN 0954-139X.
  29. ^ Inkster, Teresa; Cordina, Claire; Siegmeth, Alexander (2011-09-01). "Septic arthritis following anterior cruciate ligament reconstruction secondary to Clostridium sporogenes; a rare clinical pathogen". Journal of Clinical Pathology. 64 (9): 820–821. doi:10.1136/jcp.2010.084434. ISSN 0021-9746. PMID 21278393.
  30. ^ Safdar, H.; Gandhi, M.; Abu Khalaf, S.; Patil, S. (May 2023). "Clostridium Sporogenes: A Rare but Potent Pathogen". American Thoracic Society: A5370–A5370. doi:10.1164/ajrccm-conference.2023.207.1_MeetingAbstracts.A5370. {{cite journal}}: Cite journal requires |journal= (help)
  31. ^ Miskew, D. B.; Pinzur, M. S.; Pankovich, A. M. (1979). "Clostridial myonecrosis in a patient undergoing oxacillin therapy for exacerbation of chronic foot ulcers and osteomyelitis. A case report". Clinical Orthopaedics and Related Research (138): 250–253. ISSN 0009-921X. PMID 445907.
  32. ^ Kapustin, A V; Laishevtcev, A I; Ivanov, E V; Danilyuk, A V (2020-08-01). "Species diversity of Clostridia causing malignant edema in cattle". IOP Conference Series: Earth and Environmental Science. 548 (7) 072041. doi:10.1088/1755-1315/548/7/072041. ISSN 1755-1307.
  33. ^ Peek, S. F.; Semrad, S. D.; Perkins, G. A. (January 2003). "Clostridial myonecrosis in horses (37 cases 1985–2000)". Equine Veterinary Journal. 35 (1): 86–92. doi:10.2746/042516403775467513. ISSN 0425-1644.
  34. ^ Sudorgina, T. E.; Glotova, T. I.; Nefedchenko, A. V.; Koteneva, S. V.; Velker, D. A.; Glotov, A.  G. (2024-04-23). "The frequency of bacterial isolation of Clostridium spp. and their associations in various forms of clostridiosis in cattle". Siberian Herald of Agricultural Science. 54 (3): 55–62. doi:10.26898/0370-8799-2024-3-6. ISSN 2658-462X. {{cite journal}}: hair space character in |first6= at position 3 (help)
  35. ^ Shastin, P. N.; Savinov, V. A.; Laishevtsev, A. I.; Mandryka, E. D.; Fabrikantova, E. A.; Supova, A. V. (2025-06-28). "Clostridium species diversity in cattle". Veterinary Science Today. 14 (2): 194–200. doi:10.29326/2304-196X-2025-14-2-194-200. ISSN 2658-6959.
  36. ^ Williamson, Charles H. D.; Sahl, Jason W.; Smith, Theresa J.; Xie, Gary; Foley, Brian T.; Smith, Leonard A.; Fernández, Rafael A.; Lindström, Miia; Korkeala, Hannu; Keim, Paul; Foster, Jeffrey; Hill, Karen (December 2016). "Comparative genomic analyses reveal broad diversity in botulinum-toxin-producing Clostridia". BMC Genomics. 17 (1). doi:10.1186/s12864-016-2502-z. ISSN 1471-2164. PMC 4778365. PMID 26939550.
  37. ^ Weigand, Michael R.; Pena-Gonzalez, Angela; Shirey, Timothy B.; Broeker, Robin G.; Ishaq, Maliha K.; Konstantinidis, Konstantinos T.; Raphael, Brian H. (2015-08-15). "Implications of Genome-Based Discrimination between Clostridium botulinum Group I and Clostridium sporogenes Strains for Bacterial Taxonomy". Applied and Environmental Microbiology. 81 (16): 5420–5429. doi:10.1128/AEM.01159-15. PMC 4510194. PMID 26048939.
  38. ^ Smith, Theresa J; Xie, Gary; Williamson, Charles H D; Hill, Karen K; Fernández, Rafael A; Sahl, Jason W; Keim, Paul; Johnson, Shannon L (2020-03-01). Delaye, Luis (ed.). "Genomic Characterization of Newly Completed Genomes of Botulinum Neurotoxin-Producing Species from Argentina, Australia, and Africa". Genome Biology and Evolution. 12 (3): 229–242. doi:10.1093/gbe/evaa043. ISSN 1759-6653. PMC 7144720. PMID 32108238.
  39. ^ Brunt, Jason; van Vliet, Arnoud H. M.; Carter, Andrew T.; Stringer, Sandra C.; Amar, Corinne; Grant, Kathie A.; Godbole, Gauri; Peck, Michael W. (2020-09-11). "Diversity of the Genomes and Neurotoxins of Strains of Clostridium botulinum Group I and Clostridium sporogenes Associated with Foodborne, Infant and Wound Botulism". Toxins. 12 (9): 586. doi:10.3390/toxins12090586. ISSN 2072-6651. PMC 7551954. PMID 32932818.
  40. ^ Myburgh, Daniel Anton; da Silva, Nicolas Antonio; Haller-Caskie, Magdalena; Colominas, Lídia; Castanyer, Pere; Frigola, Joan; Tremoleda, Joaquim; Hölzel, Christina; Unterweger, Daniel; Nebel, Almut; Krause-Kyora, Ben (2025-12-31). "Detection of Clostridium sporogenes in a Roman-era cattle mass grave at Vilauba". Virulence. 16 (1). doi:10.1080/21505594.2025.2580731. ISSN 2150-5594. PMC 12587821. PMID 41144656.
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