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About Clostridium

General information:
Clostridium species are Gram-positive anaerobic spore-formers, representing ubiquitous bacilli commonly found throughout the world in soil, water, and gastrointestinal tracts of animals as well as humans.
From an evolutionary perspective, the anaerobic clostridia (or their archaic relatives) probably represent some of the first bacteria on Earth, with perhaps closely related aerobic bacilli evolving thereafter during the genesis of an oxygenated atmosphere.
Clostridium species have developed unique mechanisms for survival within and outside of numerous host types, as evidenced by the various diseases frequently linked to their protein toxins and spores.
The genus includes important pathogens (C. tetani, C. perfringens, C. botulinum and C. difficile), solvent producers (C. acetobutylicum and C. beijerinckii), cellulolytic strains (C. phytofermentans and C. thermocellum) and strains of importance in human physiology, bioremediation and wastewater treatment.
Characteristics:
Clostridial pathogens are well known for their ability to produce powerful toxins.
Disease:
C. botulinum: botulism.
C. difficile: antibiotic-associated diarrhea, antibiotic-associated pseudomembranous colitis.
C. perfingens: food poisoning, gas gangrene (clostridial myonecrosis), enteritis necroticans.
C. tetani: tetanus.
Selected genomes:comparative pathogenomics
C. acetobutylicum ATCC 824, 3940880 bp, NC_003030
C. beijerinckii NCIMB 8052, 6000632 bp, NC_009617
C. botulinum A str. ATCC 19397, 3863450 bp, NC_009697
C. botulinum A str. ATCC 3502, 3886916 bp, NC_009495
C. botulinum A str. Hall, 3760560 bp, NC_009698
C. botulinum A2 str. Kyoto, 4155278 bp, NC_012563
C. botulinum A3 str. Loch Maree, 3992906 bp, NC_010520
C. botulinum B str. Eklund 17B, 3800327 bp, NC_010674
C. botulinum B1 str. Okra, 3958233 bp, NC_010516
C. botulinum E3 str. Alaska E43, 3659644 bp, NC_010723
C. botulinum F str. Langeland, 3995387 bp, NC_009699
C. difficile 630, 4290252 bp, NC_009089
C. novyi NT, 2547720 bp, NC_008593
C. perfringens ATCC 13124, 3256683 bp, NC_008261
C. perfringens SM101, 2897393 bp, NC_008262
C. perfringens str. 13, 3031430 bp, NC_003366
C. tetani E88, 2799251 bp, NC_004557
C. thermocellum ATCC 27405, 3843301 bp, NC_009012
Plasmids:
C. botulinum A3 str. Loch Maree pCLK, 266785 bp, NC_010418
C. botulinum B str. Eklund 17B pCLL, 47642 bp, NC_010680
C. botulinum B1 str. Okra pCLD, 148780 bp, NC_010379
C. botulinum Ba4 str. 657 pCLJ, 270022 bp, NC_012654
C. botulinum C str. 203U28 pC2C203U28, 106981 bp, NC_012219
C. perfringens str. 13 pCP13, 54310 bp, NC_003042
C. perfringens str. NCTC 8533B4D pCP8533etx, 64753 bp, NC_011412
C. tetani E88 pE88, 74082 bp, NC_004565
Related publications:
Nolling J, et al., 2001. Genome sequence and comparative analysis of the solvent-producing bacterium Clostridium acetobutylicum. J. Bacteriol. 183(16):4823-4838.
Shimizu T, et al., 2002. Complete genome sequence of Clostridium perfringens, an anaerobic flesh-eater. Proc. Natl. Acad. Sci. USA 99(2):996-1001.
Bruggemann H, et al., 2003. The genome sequence of Clostridium tetani, the causative agent of tetanus disease. Proc. Natl. Acad. Sci. USA 100(3):1316-1321.
Sebaihia M, et al., 2006. The multidrug-resistant human pathogen Clostridium difficile has a highly mobile, mosaic genome. Nat Genet 38(7):779-786.
Myers GS, et al., 2006. Skewed genomic variability in strains of the toxigenic bacterial pathogen, Clostridium perfringens. Genome Res. 16(8):1031-1040.
Bettegowda C, et al., 2006. The genome and transcriptomes of the anti-tumor agent Clostridium novyi-NT. Nat. Biotechnol. 24(12):1573-1580.
Sebaihia M, et al., 2007. Genome sequence of a proteolytic (Group I) Clostridium botulinum strain Hall A and comparative analysis of the clostridial genomes. Genome Res 17(7):1082-1092.
Smith TJ, et al., 2007. Analysis of the neurotoxin complex genes in Clostridium botulinum A1-A4 and B1 Strains: BoNT/A3, /Ba4 and /B1 clusters are located within plasmids. PLoS ONE 2(12):e1271.
Figures:
Pathogenesis of Clostridium difficile (From: Shen A, 2012. Clostridium difficile toxins: mediators of inflammation. J Innate Immun 4:149-158.).


Major virulence factors in Clostridium:
Adherence
CbpA (Collagen binding protein A)
CD0873
CD2831
CD3246
Cwp66 (Cell wall protein 66)
CwpV (Cell wall protein V)
FbpA/Fbp68 (Fibronectin-binding protein A)
GroEL
SlpA (S-layer protein A)
Exotoxin
alpha-toxin (CpPLC) - C. perfringens
alpha-toxin (novyi) - C. novyi
alpha-toxin (septicum) - C. septicum
beta-toxin (CPB) - C. perfringens
beta2-toxin - C. perfringens
BoNT (Botulinum neurotoxin) - C. botulinum
C2 toxin - C. botulinum
C3 toxin - C. botulinum
CDT (Clostridium difficile toxin)
CPE (Clostridium perfringens enterotoxin) - C. perfringens
epsilon-toxin (ETX) - C. perfringens
iota-toxin - C. perfringens
NetB (Necrotic enteritis toxin B) - C. perfringens
TcdA (Toxin A)
TcdB (Toxin B)
TeNT (Tetanus neurotoxin) - C. tetani
theta-toxin/PFO (Perfringolysin O) - C. perfringens
Exoenzyme
alpha-clostripain - C. perfringens
Collagenase - C. histolyticum
Cwp84 (Cell wall protein 84)
kappa-toxin - C. perfringens
mu-toxin - C. perfringens
Sialidase - C. perfringens
Zmp1

Genomic location of virulence-related genes in Clostridium:


Reported anti-virulence compounds to Clostridium:
Alkaloids and derivatives
Protoberberine alkaloids and derivatives
Benzenoids
Benzene and substituted derivatives
Naphthalenes
Phenol ethers
Phenols
Lipids and lipid-like molecules
Prenol lipids
Organic acids and derivatives
Carboxylic acids and derivatives
Organic phosphonic acids and derivatives
Organoheterocyclic compounds
Benzodiazepines
Benzofurans
Benzothiazepines
Diazanaphthalenes
Diazinanes
Diazines
Pyridines and derivatives
Quinolines and derivatives
Thienopyridines
Phenylpropanoids and polyketides
2-arylbenzofuran flavonoids
Chalcones and dihydrochalcones
Diarylheptanoids
Flavonoids
Isoflavonoids

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