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Review

Molecular Basis of Early Stages of Clostridium difficile Infection: Germination and Colonization

Mahfuzur R Sarker1 Department of Microbiology, College of Science, Oregon State University, Corvallis, OR97331, USA;2 Department of Biomedical Sciences, College of Veterinary Medicine, Oregon State University, Corvallis, OR97331, USA
&
Daniel Paredes-Sabja2 Department of Biomedical Sciences, College of Veterinary Medicine, Oregon State University, Corvallis, OR97331, USA;3 Laboratorio de Mecanismos de Patogénesis Bacteriana, Departamento de Ciencias Biológicas, Facultad de Ciencias Biológicas, Universidad Andrés Bello, Santiago, Chile.Correspondence[email protected]
Pages 933-943 | Published online: 23 Aug 2012

References

  • Deneve C , JanoirC, PoilaneI, FantinatoC, CollignonA. New trends in Clostridium difficile virulence and pathogenesis. Int. J. Antimicrob. Agents33(Suppl. 1) , S24–S28 (2009).
  • Kuijper EJ , CoignardB, TullP. Emergence of Clostridium difficile-associated disease in North America and Europe. Clin. Microbiol. Infect.12(Suppl. 6) , 2–18 (2006).
  • Borgmann S , KistM, JakobiakT et al. Increased number of Clostridium difficile infections and prevalence of Clostridium difficile PCR ribotype 001 in southern Germany. Euro Surveill. 13(49) , (2008).
  • Herrera P , CoteraA, FicaA, GaldoT, AlvoM. [High incidence and complications of Clostridium difficile diarrhea among patients with renal diseases]. Rev. Med. Chil.131(4) , 397–403 (2003).
  • Hookman P , BarkinJS. Clostridium difficile associated infection, diarrhea and colitis. World J. Gastroenterol.15(13) , 1554–1580 (2009).
  • Loo VG , PoirierL, MillerMA et al. A predominantly clonal multi-institutional outbreak of Clostridium difficile-associated diarrhea with high morbidity and mortality. N. Engl. J. Med. 353(23) , 2442–2449 (2005).
  • Zilberberg MD , ShorrAF, KollefMH. Increase in adult Clostrdium difficile-related hospitalizations and case-fatality rate, United States, 2000–2005. Emerg. Infect. Dis.14 , 929–931 (2008).
  • Karas JA , EnochDA, AliyuSH. A review of mortality due to Clostridium difficile infection. J. Infect.61(1) , 1–8 (2010).
  • Mcfarland LV . Alternative treatments for Clostridium difficile disease: what really works? J. Med. Microbiol.54(Pt 2) , 101–111 (2005).
  • Mcfarland LV , SurawiczCM, GreenbergRN et al. A randomized placebo-controlled trial of Saccharomyces boulardii in combination with standard antibiotics for Clostridium difficile disease. JAMA 271(24) , 1913–1918 (1994).
  • Mcfarland LV , ElmerGW, SurawiczCM. Breaking the cycle: treatment strategies for 163 cases of recurrent Clostridium difficile disease. Am. J. Gastroenterol.97(7) , 1769–1775 (2002).
  • Baines SD , O‘ConnorR, SaxtonK, FreemanJ, WilcoxMH. Activity of vancomycin against epidemic Clostridium difficile strains in a human gut model. J. Antimicrob. Chemother.63(3) , 520–525 (2009).
  • Pepin J , ValiquetteL, CossetteB. Mortality attributable to nosocominal Clostridium difficile-associated disease during epidemic caused by a hypervirulent strain in Quebec. CMAJ173 , 1037–1042 (2005).
  • Pepin J , SahebN, CoulombeMA et al. Emergence of fluoroquinolones as the predominant risk factor for Clostridium difficile-associated diarrhea: a cohort study during an epidemic in Quebec. Clin. Infect. Dis. 41 , 1254–1260 (2005).
  • Rupnik M , WilcoxMH, GerdingDN. Clostridium difficile infection: new developments in epidemiology and pathogenesis. Nat. Rev. Microbiol.7(7) , 526–536 (2009).
  • Kuehne SA , CartmanST, HeapJT, KellyML, CockayneA, MintonNP. The role of toxin A and toxin B in Clostridium difficile infection. Nature467(7316) , 711–713 (2010).
  • Kuehne SA , CartmanST, MintonNP. Both, toxin A and toxin B, are important in Clostridium difficile infection. Gut Microbes2(4) , (2011).
  • Lyras D , O‘ConnorJR, HowarthPM et al. Toxin B is essential for virulence of Clostridium difficile. Nature458(7242) , 1176–1179 (2009).
  • Carter GP , AwadMM, KellyML, RoodJI, LyrasD. TcdB or not TcdB: a tale of two Clostridium difficile toxins. Future Microbiol.6 , 121–123 (2011).
  • Just I , SelzerJ, WilmM, Von Eichel-Streiber C, Mann M, Aktories K. Glucosylation of Rho proteins by Clostridium difficile toxin B. Nature375(6531) , 500–503 (1995).
  • Jank T , GiesemannT, AktoriesK. Rho-glucosylating Clostridium difficile toxins A and B: new insights into structure and function. Glycobiology17(4) , 15R–22R (2007).
  • Goncalves C , DecreD, BarbutF, BurghofferB, PetitJC. Prevalence and characterization of a binary toxin (actin-specific ADP-ribosyltransferase) from Clostridium difficile. J. Clin. Microbiol.42(5) , 1933–1939 (2004).
  • Geric B , CarmanRJ, RupnikM et al. Binary toxin-producing, large clostridial toxin-negative Clostridium difficile strains are enterotoxic but do not cause disease in hamsters. J. Infect. Dis. 193(8) , 1143–1150 (2006).
  • Schwan C , StecherB, TzivelekidisT et al. Clostridium difficile toxin CDT induces formation of microtubule-based protrusions and increases adherence of bacteria. PLoS Pathog.5(10) , e1000626 (2009).
  • Goorhuis A , BakkerD, CorverJ et al. Emergence of Clostridium difficile infection due to a new hypervirulent strain, polymerase chain reaction ribotype 078. Clin. Infect. Dis. 47(9) , 1162–1170 (2008).
  • Vonberg RP , KuijperEJ, WilcoxMH et al. Infection control measures to limit the spread of Clostridium difficile. Clin. Microbiol. Infect. 14(Suppl. 5) , 2–20 (2008).
  • Fawley WN , UnderwoodS, FreemanJ et al. Efficacy of hospital cleaning agents and germicides against epidemic Clostridium difficile strains. Infect. Control Hosp. Epidemiol. 28(8) , 920–925 (2007).
  • Riggs MM , SethiAK, ZabarskyTF, EcksteinEC, JumpRL, DonskeyCJ. Asymptomatic carriers are a potential source for transmission of epidemic and nonepidemic Clostridium difficile strains among long-term care facility residents. Clin. Infect. Dis.45(8) , 992–998 (2007).
  • Gerding DN , MutoCA, OwensRC Jr. Measures to control and prevent Clostridium difficile infection. Clin. Infect. Dis.46(Suppl. 1) , S43–S49 (2008).
  • Jump RL , PultzMJ, DonskeyCJ. 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.51(8) , 2883–2887 (2007).
  • Paredes-Sabja D , SetlowP, SarkerMR. Germination of spores of Bacillales and Clostridiales species: mechanisms and proteins involved. Trends Microbiol19(2) , 85–94 (2011).
  • Setlow P . Spore germination. Curr. Opin. Microbiol.6(6) , 550–556 (2003).
  • Wilson KH . Efficiency of various bile salt preparations for stimulation of Clostridium difficile spore germination. J. Clin. Microbiol.18(4) , 1017–1019 (1983).
  • Wilson KH , KennedyMJ, FeketyFR. Use of sodium taurocholate to enhance spore recovery on a medium selective for Clostridium difficile. J. Clin. Microbiol.15(3) , 443–446 (1982).
  • Sorg JA , SonensheinAL. Bile salts and glycine as co-germinants for Clostridium difficile spores. J. Bacteriol.190(7) , 2505–2512 (2008).
  • Howerton A , RamirezN, Abel-SantosE. Mapping interactions between germinants and Clostridium difficile spores. J. Bacteriol.193(1) , 274–282 (2011).
  • Wheeldon L , WorthingtonT, LambertP. Histidine acts as a co-germinant with glycine and taurocholate for Clostridium difficile spores. J. Appl. Microbiol. doi:10.1111/j.1365-2672.2011.04953.x (2011) (Epub ahead of print).
  • Giel JL , SorgJA, SonensheinAL, ZhuJ. Metabolism of bile salts in mice influences spore germination in Clostridium difficile. PLoS One5(1) , e8740 (2010).
  • Sorg JA , SonensheinAL. Chenodeoxycholate is an inhibitor of Clostridium difficile spore germination. J. Bacteriol.191(3) , 1115–1117 (2009).
  • Sorg JA , SonensheinAL. Inhibiting the initiation of Clostridium difficile spore germination using analogs of chenodeoxycholic acid, a bile acid. J. Bacteriol.192(19) , 4983–4990 (2010).
  • Mallonee DH , HylemonPB. Sequencing and expression of a gene encoding a bile acid transporter from Eubacterium sp. strain VPI 12708. J. Bacteriol.178(24) , 7053–7058 (1996).
  • Ridlon JM , KangDJ, HylemonPB. Bile salt biotransformations by human intestinal bacteria. J. Lipid Res.47(2) , 241–259 (2006).
  • Heeg D , BurnsDA, CartmanST, MintonNP. Spores of Clostridium difficile clinical isolates display a diverse germination response to bile salts. PLoS One7(2) , e32381 (2012).
  • Ramirez N , LigginsM, Abel-SantosE. Kinetic evidence for the presence of putative germination receptors in Clostridium difficile spores. J. Bacteriol.192(16) , 4215–4222 (2010).
  • Sebaihia M , WrenBW, MullanyP et al. The multidrug-resistant human pathogen Clostridium difficile has a highly mobile, mosaic genome. Nat. Genet. 38(7) , 779–786 (2006).
  • Moir A , SmithDA. The genetics of bacterial spore germination. Annu. Rev. Microbiol.44 , 531–553 (1990).
  • Paredes-Sabja D , SarkerMR. Germination response of spores of the pathoenic bacetrium Clostridium perfringens and Clostridium difficile to cultured human epithelial cells. Anaerobe17(2) , 78–84 (2011).
  • Burns DA , HeapJT, MintonNP. SleC is essential for germination of Clostridium difficile spores in nutrient-rich medium supplemented with the bile salt taurocholate. J. Bacteriol.192(3) , 657–664 (2010).
  • Cartman ST , MintonNP. A mariner-based transposon system for in vivo random mutagenesis of Clostridium difficile. Appl. Environ. Microbiol.76(4) , 1103–1109 (2010).
  • Bernet-Camard MF , CoconnierMH, HudaultS, ServinAL. Differentiation-associated antimicrobial functions in human colon adenocarcinoma cell lines. Exp. Cell Res.226(1) , 80–89 (1996).
  • Northfield TC , MccollI. Postprandial concentrations of free and conjugated bile acids down the length of the normal human small intestine. Gut14(7) , 513–518 (1973).
  • Mekhjian HS , PhillipsSF, HofmannAF. Colonic absorption of unconjugated bile acids: perfusion studies in man. Dig. Dis. Sci.24(7) , 545–550 (1979).
  • Janvilisri T , ScariaJ, ChangYF. Transcriptional profiling of Clostridium difficile and Caco-2 cells during infection. J. Infect. Dis.202(2) , 282–290 (2010).
  • Eveillard M , FourelV, BarcMC et al. Identification and characterization of adhesive factors of Clostridium difficile involved in adhesion to human colonic enterocyte-like Caco-2 and mucus-secreting HT29 cells in culture. Mol. Microbiol. 7(3) , 371–381 (1993).
  • Cerquetti M , SerafinoA, SebastianelliA, MastrantonioP. Binding of Clostridium difficile to Caco-2 epithelial cell line and to extracellular matrix proteins. FEMS Immunol. Med. Microbiol.32(3) , 211–218 (2002).
  • Sara M , SleytrUB. S-Layer proteins. J. Bacteriol.182(4) , 859–868 (2000).
  • Cerquetti M , MolinariA, SebastianelliA et al. Characterization of surface layer proteins from different Clostridium difficile clinical isolates. Microb. Pathog. 28(6) , 363–372 (2000).
  • Calabi E , WardS, WrenB et al. Molecular characterization of the surface layer proteins from Clostridium difficile. Mol. Microbiol.40(5) , 1187–1199 (2001).
  • Qazi O , HitchenP, TissotB et al. Mass spectrometric analysis of the S-layer proteins from Clostridium difficile demonstrates the absence of glycosylation. J. Mass Spectrom. 44(3) , 368–374 (2009).
  • Takeoka A , TakumiK, KogaT, KawataT. Purification and characterization of S layer proteins from Clostridium difficile GAI 0714. J. Gen. Microbiol.137(2) , 261–267 (1991).
  • Calabi E , CalabiF, PhillipsAD, FairweatherNF. Binding of Clostridium difficile surface layer proteins to gastrointestinal tissues. Infect. Immun.70(10) , 5770–5778 (2002).
  • Fagan RP , Albesa-JoveD, QaziO, SvergunDI, BrownKA, FairweatherNF. Structural insights into the molecular organization of the S-layer from Clostridium difficile. Mol Microbiol71(5) , 1308–1322 (2009).
  • Spigaglia P , BarbantiF, MastrantonioP. Surface layer protein A variant of Clostridium difficile PCR-ribotype 027. Emerg. Infect. Dis.17(2) , 317–319 (2011).
  • Spigaglia P , GaleottiCL, BarbantiF, ScarselliM, Van Broeck J, Mastrantonio P. Clostridium difficile PCR-ribotypes 027 and 001 share common immunogenic properties of the low-molecular-weight (LMW) surface layer (S-layer) protein. J. Med. Microbiol.60(Pt 8) , 1168–1173 (2011).
  • Maeda H . Role of microbial proteases in pathogenesis. Microbiol. Immunol.40(10) , 685–699 (1996).
  • Matsumoto K . Role of bacterial proteases in pseudomonal and serratial keratitis. Biol. Chem.385(11) , 1007–1016 (2004).
  • Savariau-Lacomme MP , LebarbierC, KarjalainenT, CollignonA, JanoirC. Transcription and analysis of polymorphism in a cluster of genes encoding surface-associated proteins of Clostridium difficile. J. Bacteriol.185(15) , 4461–4470 (2003).
  • Janoir C , PechineS, GrosdidierC, CollignonA. Cwp84, a surface-associated protein of Clostridium difficile, is a cysteine protease with degrading activity on extracellular matrix proteins. J. Bacteriol.189(20) , 7174–7180 (2007).
  • Kirby JM , AhernH, RobertsAK et al. Cwp84, a surface-associated cysteine protease, plays a role in the maturation of the surface layer of Clostridium difficile. J. Biol. Chem. 284(50) , 34666–34673 (2009).
  • Fagan RP , JanoirC, CollignonA, MastrantonioP, PoxtonIR, FairweatherNF. A proposed nomenclature for cell wall proteins of Clostridium difficile. J. Med. Microbiol.60(Pt 8) , 1225–1228 (2011).
  • Chapetonmontes D , CandelaT, CollignonA, JanoirC. Localization of the Clostridium difficile cysteine protease Cwp84 and insights into its maturation process. J. Bacteriol.193(19) , 5314–5321 (2011).
  • De La Riva L , WillingSE, TateEW, FairweatherNF. Roles of cysteine proteases Cwp84 and Cwp13 in biogenesis of the cell wall of Clostridium difficile. J. Bacteriol.193(13) , 3276–3285 (2011).
  • Reynolds CB , EmersonJE, De La Riva L, Fagan RP, Fairweather NF. The Clostridium difficile cell wall protein CwpV is antigenically variable between strains, but exhibits conserved aggregation-promoting function. PLoS Pathog.7(4) , e1002024 (2011).
  • Emerson JE , ReynoldsCB, FaganRP, ShawHA, GouldingD, FairweatherNF. A novel genetic switch controls phase variable expression of CwpV, a Clostridium difficile cell wall protein. Mol. Microbiol.74(3) , 541–556 (2009).
  • Waligora AJ , HennequinC, MullanyP, BourliouxP, CollignonA, KarjalainenT. Characterization of a cell surface protein of Clostridium difficile with adhesive properties. Infect. Immun.69(4) , 2144–2153 (2001).
  • Kuboniwa M , AmanoA, HashinoE et al. Distinct roles of long/short fimbriae and gingipains in homotypic biofilm development by Porphyromonas gingivalis. BMC Microbiol. 9 , 105 (2009).
  • Lawley TD , ClareS, WalkerAW et al. Antibiotic treatment of Clostridium difficile carrier mice triggers a supershedder state, spore-mediated transmission, and severe disease in immunocompromised hosts. Infect. Immun. 77(9) , 3661–3669 (2009).
  • Saujet L , MonotM, DupuyB, SoutourinaO, Martin-VerstraeteI. The key sigma factor of transition phase, SigH, controls sporulation, metabolism, and virulence factor expression in Clostridium difficile. J. Bacteriol.193(13) , 3186–3196 (2011).
  • Hennequin C , PorcherayF, Waligora-DuprietA et al. GroEL (Hsp60) of Clostridium difficile is involved in cell adherence. Microbiology 147(Pt 1) , 87–96 (2001).
  • Hennequin C , CollignonA, KarjalainenT. Analysis of expression of GroEL (Hsp60) of Clostridium difficile in response to stress. Microb. Pathog.31(5) , 255–260 (2001).
  • Jain S , GrahamC, GrahamRL, McmullanG, TernanNG. Quantitative proteomic analysis of the heat stress response in Clostridium difficile strain 630. J. Proteome Res.10(9) , 3880–3890 (2011).
  • Tasteyre A , BarcMC, CollignonA, BoureauH, KarjalainenT. Role of FliC and FliD flagellar proteins of Clostridium difficile in adherence and gut colonization. Infect. Immun.69(12) , 7937–7940 (2001).
  • Twine SM , ReidCW, AubryA et al. Motility and flagellar glycosylation in Clostridium difficile. J. Bacteriol.191(22) , 7050–7062 (2009).
  • Dietrich C , HeunerK, BrandBC, HackerJ, SteinertM. Flagellum of Legionella pneumophila positively affects the early phase of infection of eukaryotic host cells. Infect. Immun.69(4) , 2116–2122 (2001).
  • Grant CC , KonkelME, CieplakW Jr, Tompkins LS. Role of flagella in adherence, internalization, and translocation of Campylobacter jejuni in nonpolarized and polarized epithelial cell cultures. Infect. Immun.61(5) , 1764–1771 (1993).
  • Mcsweegan E , WalkerRI. Identification and characterization of two Campylobacter jejuni adhesins for cellular and mucous substrates. Infect. Immun.53(1) , 141–148 (1986).
  • Eaton KA , SuerbaumS, JosenhansC, KrakowkaS. Colonization of gnotobiotic piglets by Helicobacter pylori deficient in two flagellin genes. Infect. Immun.64(7) , 2445–2448 (1996).
  • Rabaan AA , GryllosI, TomasJM, ShawJG. Motility and the polar flagellum are required for Aeromonas caviae adherence to HEp-2 cells. Infect. Immun.69(7) , 4257–4267 (2001).
  • Dingle TC , MulveyGL, ArmstrongGD. Mutagenic analysis of the Clostridium difficile flagellar proteins, FliC and FliD, and their contribution to virulence in hamsters. Infect Immun.79(10) , 4061–4067 (2011).
  • Seddon SV , HemingwayI, BorrielloSP. Hydrolytic enzyme production by Clostridium difficile and its relationship to toxin production and virulence in the hamster model. J. Med. Microbiol.31(3) , 169–174 (1990).
  • Poilane I , KarjalainenT, BarcMC, BourliouxP, CollignonA. Protease activity of Clostridium difficile strains. Can. J. Microbiol.44(2) , 157–161 (1998).
  • Janvilisri T , ScariaJ, ThompsonAD et al. Microarray identification of Clostridium difficile core components and divergent regions associated with host origin. J. Bacteriol. 191(12) , 3881–3891 (2009).
  • Timpl R , BrownJC. Supramolecular assembly of basement membranes. Bioessays18(2) , 123–132 (1996).
  • Henderson B , NairS, PallasJ, WilliamsMA. Fibronectin: a multidomain host adhesin targeted by bacterial fibronectin-binding proteins. FEMS Microbiol. Rev.35(1) , 147–200 (2011).
  • Courtney HS , LiY, DaleJB, HastyDL. Cloning, sequencing, and expression of a fibronectin/fibrinogen-binding protein from group A streptococci. Infect. Immun.62(9) , 3937–3946 (1994).
  • Van Der Flier M , ChhunN, WizemannTM, MinJ, MccarthyJB, TuomanenEI. Adherence of Streptococcus pneumoniae to immobilized fibronectin. Infect. Immun.63(11) , 4317–4322 (1995).
  • Hennequin C , JanoirC, BarcMC, CollignonA, KarjalainenT. Identification and characterization of a fibronectin-binding protein from Clostridium difficile. Microbiology149(Pt 10) , 2779–2787 (2003).
  • Lin YP , KuoCJ, KoleciX, McdonoughSP, ChangYF. Manganese binds to Clostridium difficile Fbp68 and is essential for fibronectin binding. J. Biol. Chem.286(5) , 3957–3969 (2011).
  • Barketi-Klai A , HoysS, Lambert-BordesS, CollignonA, KansauI. Role of fibronectin binding protein A in Clostridium difficile intestinal colonization. J. Med. Microbiol.60(Pt 8) , 1155–1161 (2011).
  • Van Der Woude MW , BaumlerAJ. Phase and antigenic variation in bacteria. Clin. Microb. Rev.17(3) , 581–611 (2004).
  • Ho TD , EllermeierCD. PrsW is required for colonization, resistance to antimicrobial peptides, and expression of extracytoplasmic function sigma factors in Clostridium difficile. Infect. Immun.79(8) , 3229–3238 (2011).
  • Mcbride SM , SonensheinAL. The dlt operon confers resistance to cationic antimicrobial peptides in Clostridium difficile. Microbiology157(Pt 5) , 1457–1465 (2011).
  • Hasegawa M , YamazakiT, KamadaN et al. Nucleotide-binding oligomerization domain 1 mediates recognition of Clostridium difficile and induces neutrophil recruitment and protection against the pathogen. J. Immunol. 186(8) , 4872–4880 (2011).
  • Ryan A , LynchM, SmithSM et al. A role for TLR4 in Clostridium difficile infection and the recognition of surface layer proteins. PLoS Pathog. 7(6) , e1002076 (2011).
  • Drudy D , CalabiE, KyneL et al. Human antibody response to surface layer proteins in Clostridium difficile infection. FEMS Immunol. Med. Microbiol. 41(3) , 237–242 (2004).

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