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PMID: 18245298 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Bile salts and glycine as cogerminants for Clostridium difficile spores.

Journal of bacteriology ·Vol. 190 ·No. 7 ·2008-04-00 ·Pages 2505-12

Sorg JA, Sonenshein AL

Abstract

Spore formation by Clostridium difficile is a significant obstacle to overcoming hospital-acquired C. difficile-associated disease. Spores are resistant to heat, radiation, chemicals, and antibiotics, making a contaminated environment difficult to clean. To cause disease, however, spores must germinate and grow out as vegetative cells. The germination of C. difficile spores has not been examined in detail. In an effort to understand the germination of C. difficile spores, we characterized the response of C. difficile spores to bile. We found that cholate derivatives and the amino acid glycine act as cogerminants. Deoxycholate, a metabolite of cholate produced by the normal intestinal flora, also induced germination of C. difficile spores but prevented the growth of vegetative C. difficile. A model of resistance to C. difficile colonization mediated by the normal bacterial flora is proposed.

MeSH Terms
Bile Acids and Salts/chemistry,pharmacology Cholates/chemistry,pharmacology Clostridioides difficile/drug effects,physiology Deoxycholic Acid/chemistry,pharmacology Glycine/chemistry,pharmacology Glycocholic Acid/chemistry,pharmacology Molecular Structure Spores, Bacterial/drug effects,physiology Taurocholic Acid/chemistry,pharmacology
Chemicals
Bile Acids and Salts Cholates Deoxycholic Acid Taurocholic Acid Glycocholic Acid Glycine
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Sorg Joseph A
Department of Molecular Biology and Microbiology, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111, USA.
Sonenshein Abraham L
References (43)
43 references, click to expand
  1. Exosporial membrane plasticity of Clostridium sporogenes and Clostridium difficile.
    Tissue Cell. 1997 Aug;29(4):449-61 PMID: 9281845
  2. Role of competition for nutrients in suppression of Clostridium difficile by the colonic microflora.
    Infect Immun. 1988 Oct;56(10):2610-4 PMID: 3417352
  3. Bile salt biotransformations by human intestinal bacteria.
    J Lipid Res. 2006 Feb;47(2):241-59 PMID: 16299351
  4. Pseudomembranous colitis: causes and cures.
    Digestion. 1999 Mar-Apr;60(2):91-100 PMID: 10095149
  5. A comparative genomic view of clostridial sporulation and physiology.
    Nat Rev Microbiol. 2005 Dec;3(12):969-78 PMID: 16261177
  6. Bile salt hydrolase activity of three strains of Lactobacillus acidophilus.
    J Dairy Sci. 1999 Mar;82(3):472-80 PMID: 10194664
  7. Compartmentalization of gene expression during Bacillus subtilis spore formation.
    Microbiol Mol Biol Rev. 2004 Jun;68(2):234-62 PMID: 15187183
  8. Bile acid metabolism by fresh human colonic contents: a comparison of caecal versus faecal samples.
    Gut. 2001 Dec;49(6):835-42 PMID: 11709519
  9. The emerging infectious challenge of clostridium difficile-associated disease in Massachusetts hospitals: clinical and economic consequences.
    Infect Control Hosp Epidemiol. 2007 Nov;28(11):1219-27 PMID: 17926270
  10. Clostridium difficile toxins: mechanism of action and role in disease.
    Clin Microbiol Rev. 2005 Apr;18(2):247-63 PMID: 15831824
  11. Quantitative analysis of fecal bile acids by gas-liquid chromatography.
    Anal Biochem. 1963 Jun;5:523-30 PMID: 13932373
  12. Actin-specific ADP-ribosyltransferase produced by a Clostridium difficile strain.
    Infect Immun. 1988 Sep;56(9):2299-306 PMID: 3137166
  13. Isolation of environmental Clostridium difficile from a veterinary teaching hospital.
    J Vet Diagn Invest. 2000 Sep;12(5):449-52 PMID: 11021433
  14. In vitro killing of nosocomial pathogens by acid and acidified nitrite.
    Antimicrob Agents Chemother. 2006 Nov;50(11):3901-4 PMID: 17065628
  15. Bile acid induction specificity of 7 alpha-dehydroxylase activity in an intestinal Eubacterium species.
    Steroids. 1980 Jan;35(1):103-9 PMID: 7376208
  16. Sequencing and expression of a gene encoding a bile acid transporter from Eubacterium sp. strain VPI 12708.
    J Bacteriol. 1996 Dec;178(24):7053-8 PMID: 8955384
  17. Efficiency of various bile salt preparations for stimulation of Clostridium difficile spore germination.
    J Clin Microbiol. 1983 Oct;18(4):1017-9 PMID: 6630458
  18. Biochemistry of L-proline-triggered germination of Bacillus megaterium spores.
    J Bacteriol. 1979 May;138(2):431-41 PMID: 35526
  19. The multidrug-resistant human pathogen Clostridium difficile has a highly mobile, mosaic genome.
    Nat Genet. 2006 Jul;38(7):779-86 PMID: 16804543
  20. Identification and characterization of a bile acid 7alpha-dehydroxylation operon in Clostridium sp. strain TO-931, a highly active 7alpha-dehydroxylating strain isolated from human feces.
    Appl Environ Microbiol. 2000 Mar;66(3):1107-13 PMID: 10698778
  21. Effect of neomycin and other antibiotics on serum cholesterol levels and on 7alpha-dehydroxylation of bile acids by the fecal bacterial flora in man.
    Circ Res. 1973 Oct;33(4):393-402 PMID: 4741941
  22. Separation of two functional roles of L-alanine in the initiation of Bacillus subtilis spore germination.
    J Bacteriol. 1967 Sep;94(3):522-9 PMID: 4962298
  23. Structure, assembly, and function of the spore surface layers.
    Annu Rev Microbiol. 2007;61:555-88 PMID: 18035610
  24. Spore germination.
    Curr Opin Microbiol. 2003 Dec;6(6):550-6 PMID: 14662349
  25. Growth, sporulation and enterotoxin production by Clostridium perfringens type A in the presence of human bile salts.
    FEMS Microbiol Lett. 1991 Nov 1;68(1):15-21 PMID: 1769549
  26. Comparison of cycloserine-cefoxitin-fructose agar (CCFA) and taurocholate-CCFA for recovery of Clostridium difficile during surveillance of hospitalized patients.
    Diagn Microbiol Infect Dis. 1997 Sep;29(1):1-4 PMID: 9350408
  27. Genetics analysis of spore germination mutants of Bacillus subtilis 168: the correlation of phenotype with map location.
    J Gen Microbiol. 1979 Mar;111(1):165-80 PMID: 110906
  28. Clindamycin-induced enterocolitis in hamsters.
    J Infect Dis. 1978 Apr;137(4):464-75 PMID: 649990
  29. The spectrum of pseudomembranous enterocolitis and antibiotic-associated diarrhea.
    Arch Intern Med. 2002 Oct 28;162(19):2177-84 PMID: 12390059
  30. Efficient sporulation in Clostridium difficile requires disruption of the sigmaK gene.
    Mol Microbiol. 2003 May;48(3):811-21 PMID: 12694623
  31. Implantation of bacteria from the digestive tract of man and various animals into gnotobiotic mice.
    Am J Clin Nutr. 1980 Nov;33(11 Suppl):2440-7 PMID: 7001883
  32. Amino acid- and purine ribonucleoside-induced germination of Bacillus anthracis DeltaSterne endospores: gerS mediates responses to aromatic ring structures.
    J Bacteriol. 2002 Mar;184(5):1296-303 PMID: 11844758
  33. The genetics of bacterial spore germination.
    Annu Rev Microbiol. 1990;44:531-53 PMID: 2252393
  34. Purification and characterization of bile salt hydrolase from Clostridium perfringens.
    J Lipid Res. 1988 Aug;29(8):1079-85 PMID: 2903208
  35. Identification and characterization of sporulation-dependent promoters upstream of the enterotoxin gene (cpe) of Clostridium perfringens.
    J Bacteriol. 1998 Jan;180(1):136-42 PMID: 9422603
  36. Identification of an in vivo inhibitor of Bacillus anthracis spore germination.
    J Biol Chem. 2007 Apr 20;282(16):12112-8 PMID: 17296608
  37. Postprandial concentrations of free and conjugated bile acids down the length of the normal human small intestine.
    Gut. 1973 Jul;14(7):513-8 PMID: 4729918
  38. Recovery of spores of Clostridium difficile altered by heat or alkali.
    J Med Microbiol. 1989 Mar;28(3):217-21 PMID: 2926793
  39. Vegetative Clostridium difficile survives in room air on moist surfaces and in gastric contents with reduced acidity: a potential mechanism to explain the association between proton pump inhibitors and C. difficile-associated diarrhea?
    Antimicrob Agents Chemother. 2007 Aug;51(8):2883-7 PMID: 17562803
  40. Use of sodium taurocholate to enhance spore recovery on a medium selective for Clostridium difficile.
    J Clin Microbiol. 1982 Mar;15(3):443-6 PMID: 7076817
  41. Suppression of toxin production in Clostridium difficile VPI 10463 by amino acids.
    Microbiology (Reading). 1999 Jul;145 ( Pt 7):1683-1693 PMID: 10439407
  42. Human cecal bile acids: concentration and spectrum.
    Am J Physiol Gastrointest Liver Physiol. 2007 Jul;293(1):G256-63 PMID: 17412828
  43. Isolation of deoxycholic acid from normal human feces.
    J Biol Chem. 1955 Oct;216(2):847-50 PMID: 13271359
Article Info
Journal
Journal of bacteriology
Abbr.
J Bacteriol
ISSN
1098-5530
Published
2008-04-00
Epub
2008-00-01
Pages
2505-12
Language
English
Region
United States
NLM ID
2985120R
PMCID
PMC2293200
Subset
IM
Grants
NIGMS NIH HHS · K12 GM074869-02 · United States
NIAID NIH HHS · N01AI30050 · United States
NIGMS NIH HHS · K12 GM074869 · United States
NIAID NIH HHS · N01-AI-30050 · United States
NIGMS NIH HHS · R01 GM042219 · United States
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