LCTs are homologous toxins that inactivate host Rho and Ras family guanosine triphosphatases (GTPase) by glucosylation. no indication that the presence of the bacteria had any deleterious effects on the newborns. Thus, for the next four decades remained a little known bacterium that was considered a part of the normal intestinal flora of infants. was the causative agent (Lyerly et al., 1988). Moreover, the toxic secreted components that Hall and O’Toole noted in filtrates from cultures were implicated in causing PMC. The toxic components were identified as two proteins, toxin A (TcdA) and toxin B (TcdB). Although the pathogenicity of toward humans was first discovered in relation to its ability to cause PMC, it is now known that the manifestations of infection can range from asymptomatic carriage, to mild diarrhea, to life-threatening conditions such as PMC and toxic megacolon. Collectively, the manifestations of disease caused by are referred to as associated disease (CDAD). Sohn et al. have estimated that there are 7 CDAD case patients per 1,000 admissions in acute care hospitals (Sohn et al., 2005). It (E)-Ferulic acid should be noted, however, that burden varies dramatically by geographic region, between institutions, and even between wards of the same hospital (Lyerly et al., 1988; Bartlett, 1994; Sohn et al., 2005; McDonald et al., 2007). Total costs of to the US health care system are thought to exceed $3 billion per year (Kyne et al., 2002; Brazier, 2008). Between the late 1990s and mid 2000s there was a dramatic increase in the number of cases of CDAD. Rates of CDAD more than doubled in many localities (Kelly and LaMont, 2008). According to death certificate data, related deaths in the US rose from 5.7 deaths per million in the population in 1999 to 23.7 in 2004 (Redelings et al., 2007). This vast upsurge in CDAD has been primarily attributed to the emergence of more virulent strains categorized as North American pulsotype 1/PCR-ribotype 027 (NAP1/027). NAP1/027 strains have been reported to have higher production of TcdA and TcdB (Warny et al., 2005), a more cytopathic form of TcdB (Stabler et al., 2008; Lanis et al., 2010), production of (E)-Ferulic acid binary toxin (McDonald et al., LSH 2005), higher rates of sporulation (Merrigan et al., 2003; Akerlund et al., 2008), and increased antibiotic resistance (McDonald et al., 2005). Virulence factors of (E)-Ferulic acid C. difficile Several factors have been implicated in the virulence of including adhesins (Waligora et al., 2001), extracellular enzymes (Savariau-Lacomme et al., 2003), fimbrae (Borriello et al., 1990), flagella (Delmee et al., 1990; Stabler et al., 2006), capsule (Borriello et al., 1990), and a paracrystalline S-layer (Karjalainen et al., 2001; Sebaihia et al., 2006). In addition, produces three secreted protein toxins: TcdA, TcdB, and the binary toxin CDTab. CDTab is an actin-specific ADP-ribosyltransferase that is homologous to iota toxin from (Popoff et al., 1988; Perelle et al., 1997). Many pathogenic strains do not produce CDTab (Rupnik et al., 2003), and the role of binary toxin in pathogenesis is unclear (Perelle et al., 1997; Barbut et al., 2005; Geric et al., 2006). TcdA and TcdB are 308 and 270 kDa proteins, respectively, with 49% (E)-Ferulic acid identity and 63% similarity. They belong to a larger family of large clostridial toxins (LCTs) which includes lethal and hemorrhagic toxins from (TcsL and TcsH), -toxin from (Tcn), and large cytotoxin from (TpeL) (Table ?(Table1).1). LCTs are homologous toxins that inactivate host Rho and Ras family guanosine triphosphatases (GTPase) by glucosylation. The Rho and Ras family GTPases are master regulators of a number of vital cellular processes including cycle progression, cell-cell adhesion, cytokinesis, secretion, and maintenance of the cytoskeleton (Bishop and Hall, 2000; Jank et.