, 2005; Green et al., 2007; Marcos & DuPont, 2007), has come to light. The strain carries Cyclopamine the binary toxin gene CdtB, and has an 18-base-pair deletion in the toxin repressor gene, tcdC, which means that it generates approximately 16–23 times more toxin than other strains (Warny et al., 2005). Infection is associated with a high risk of acute clinical deterioration and a poor response to metronidazole
therapy (Spigaglia & Mastrantonio, 2002; Pepin et al., 2005), making it a major concern for healthcare worldwide. Clostridium difficile ribotype 027 was initially rare in the United Kingdom; however, when outbreaks at Stoke Mandeville and the Royal Devon and Exeter Hospitals were investigated in 2004–2005, type 027 was found to predominate in their cases (Anon, 2006), MK-2206 price and this ribotype has now been detected in the majority of countries around the world (Kuijper et al., 2007). It is clear, then, that C. difficile is a significant burden on the healthcare profession and patients. With the ever-increasing availability of genomic information, however, greater insight into the evolution and variation of C.
difficile genomes is now possible (Stabler et al., 2006, 2009; He et al., 2010). The Clostridb database (http://xbase.bham.ac.uk/clostridb/) (Chaudhuri & Pallen, 2006), an excellent publicly accessible resource for those interested in comparative genomics of the genus Clostridium, currently contains genome sequences of 18 strains of clostridia, including two genomes of C. difficile, namely C. difficile 630 and C. difficile qcd32_g58, a representative of the predominant
NAP1/BI/027 strain in Quebec (Loo et al., 2005). The 4.29 Mb genome of C. difficile strain 630 and its Celastrol 7.8 kb plasmid encode a remarkable number of genes associated with resistance to antimicrobial agents, as well as virulence factors, host adherents and surface structures (Sebaihia et al., 2007). Genome sequences have been generated recently for a further six strains, including CD196, an early, nonepidemic, ribotype 027 strain (Stabler et al., 2009), the R20291 isolate responsible for the UK Stoke Mandeville outbreak, and 21 other hypervirulent ribotype 027 strains isolated over the past two decades (He et al., 2010). A further six hypervirulent isolates associated with the Quebec outbreak and a reference ATCC43255 strain are at the draft genome sequence stage (McGill University and Génome Québec Innovation Centre), while the human microbiome project at Baylor College of Medicine has draft genome sequences for two strains (NAP07, NAP08) at the time of writing. These genomic data, along with recently developed tools for Clostridial functional genomics (Heap et al., 2009), make it possible for researchers to adopt a systems approach to the dissection of the physiology and biochemistry of this pathogen.