A Microbial Biorealm page on the genus Clostridium difficile
Higher order taxa
Bacteria; Firmicutes; Clostridia; Clostridiales; Clostridiaceae; Clostridium [Others may be used. Use  link to find]
Description and significance
Cell structure and metabolism
Describe any interesting features and/or cell structures; how it gains energy; what important molecules it produces.
C. difficile is a gram-positive spore-forming anaerobe. It expresses two S-layer proteins one of which is highly conserved among strains and one which shows sequence diversity. Both proteins are derived from a single gene product and both are associated with amidase activity. It requires five amino acids (Leu, Ile, Pro, Trp and Val) for energy metabolism and addition of Gly increases growth significantly. C. difficile undergoes amino acid fermentation in order to create ATP as a source of energy.
Describe any interactions with other organisms (included eukaryotes), contributions to the environment, effect on environment, etc.
C. difficile is not a major constituent of the microflora in colons of healthy adult humans or animals but can grow to large populations in people that are treated with antibiotics, especially broad-spectrum antibiotics. This is because the antibiotics kill off the normal flora of the intestines leaving C. difficile to freely grow and colonize the intestine. As long as other organisms are around C. difficile cannot grow due to limited resources and space, however, there is nothing stopping it from growing out of control in the absence of other microorganisms. When under extreme conditions such as the low pH environment of the stomach, high heat or when under attack by antibiotics C. difficile can form spores which can survive for up to two years and withstand extreme conditions. The spores can then convert to the active form of C. difficile when conditions are favorable and allow the bacteria to grow.
Overgrowth of the bacteria in the intestines of human and animal hosts leads to buildup of its toxins and their deleterious effects. It can be transferred from person to person through the fecal-oral route. Most often C. difficile is acquired nosocomially (contracted secondary to being hospitalized). C. difficile produces two virulence factors: enterotoxin (toxin A) which is found in 70% of strains and cytotoxin (toxin B) which is found in all strains. The toxins inactivate GTPases and disrupt tight junctions in the intestinal epithelial cells leading to increased paracellular permeability which leads to fluid secretion (diarrhea), mucosal injury and inflammation. Expression of C. difficile toxins A and B and their sigma factor TcdD is controlled by temperature; they become upregulated when the temperature is shifted from 22 to 37 degrees C which is an adaptation to their mammalian hosts C. difficile toxin B gets cleaved by a factor in the eukaryotic target cell thereby permitting its cellular uptake. Patient symptoms with C. difficile intestinal infections include diarrhea, inflammation, fever and abdominal pain. C. difficile is the primary causative agent of pseudomembranous colitis which involves many of the above mentioned systems.
Application to Biotechnology
Does this organism produce any useful compounds or enzymes? What are they and how are they used?
Enter summaries of the most recent research here--at least three required
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Kyne, L., Farrell, R.J., Kelly, C.P. “Clostridium difficile”. Gastroenterol Clin North Am. 2001 Sep;30(3):753-77, ix-x.
Bartlett, J.G. “Clostridium difficile: history of its role as an enteric pathogen and the current state of knowledge about the organism”. Clin Infect Dis. 1994 May;18 Suppl 4:S265-72.
Sebaihia, M., Wren, B.W., et al. “The multidrug-resistant human pathogen Clostridium difficile has a highly mobile, mosaic genome”. Nat Genet. 2006 Jul;38(7):779-86. Epub 2006 Jun 25.
Calabi, E., Ward, S., Wren, B., Paxton, T., Panico, M., Morris, H., Dell, A., Dougan, G., and Fairweather, N. “Molecular characterization of the surface layer proteins from Clostridium difficile”. Mol Microbiol. 2001 Jun;40(5):1187-99.
Karlsson, S., Dupuy, B., Mukherjee, K., Norin, E., Burman, L.G., and Akerlund, T. “Expression of Clostridium difficile toxins A and B and their sigma factor TcdD is controlled by temperature”. Infect Immun. 2003 Apr;71(4):1784-93.
Greco, A., Ho, J., Lin, S., Palcic, M., Rupnik, M., and Ng, K. “Carbohydrate recognition by Clostridium difficile toxin A”. Nature Structural & Molecular Biology - 13, 460 - 461 (2006)
Nusrat, A., Eichel-Streiber, C., Turner, J.R., Verkade, P., Madara, J.L., and Parkos, C.A. “Clostridium difficile Toxins Disrupt Epithelial Barrier Function by Altering Membrane Microdomain Localization of Tight Junction Proteins”. Infection and Immunity, March 2001, p. 1329-1336, Vol. 69, No. 3
Jackson, S., Calos, M., Myers, A., and Self, W. “Analysis of Proline Reduction in the Nosocomial Pathogen Clostridium difficile”. J Bacteriol. 2006 December; 188(24): 8487–8495.
Reineke, J., Tenzer, S., Rupnik, M., Koschinksi, A., Hasselmeyer, O., Schrattenholz, A., Schild, H., Eichel-Streiber, C. “Autocatalytic cleavage of Clostridium difficile toxin B”. Nature 446, 415-410, 2007
Wilson, K. “The microecology of Clostridium difficile”. Clin Infect Dis. 1993 Jun;16 Suppl 4:S214-8
Gianfrilli, P., Luzzi, I., Pantosti, A., Occhionero, M., Gentile, G., Panichi, G. “Cytotoxin and enterotoxin production by Clostridium difficile”. Microbiologica. 1984 Oct;7(4):375-9.
Rao, A., Jump, R., Pultz, N., Pultz, M., Donskey, C. “In vitro killing of nosocomial pathogens by acid and acidified nitrite”. Antimicrob Agents Chemother. 2006 Nov;50(11):3901-4.
Lebel, S., Bouttier, S., Lambert, T. “The cme gene of Clostridium difficile confers multidrug resistance in Enterococcus faecalis”. FEMS Microbiology Letters 238 (1), 93–100.
Dridi, L., Tankovic, J., Petit, J. “CdeA of Clostridium difficile, a New Multidrug Efflux Transporter of the MATE family”. Microb Drug Resist. 2004 Sept;10(3):191-6.
Hall I, O'Toole E. "Intestinal flora in newborn infants with a description of a new pathogenic anaerobe, Bacillus difficilis". Am J Dis Child 1935 49: 390.
Barth H, Aktories K, Popoff M, Stiles B. "Binary bacterial toxins: biochemistry, biology, and applications of common Clostridium and Bacillus proteins". 2004 Microbiol Mol Biol Rev 68 (3): 373-402
Paredes, C., Alsaker, K., Papoutsakis, E. “A comparative genomic view of clostridial sporulation and physiology”. Nature Reviews Microbiology 2005 3, 969-978
Tabaqchali, S., Wilks, M. “Epidemiological aspects of infections caused by Bacteroides fragilis and Clostridium difficile”. Eur J Clin Microbiol Infect Dis 1992;11:1049-57.
Edited by Shaheen Najafi student of Rachel Larsen and Kit Pogliano