difficile spores come in close proximity with the microvilli of differentiated Caco-2 cells furthermore, C. difficile spores exhibit high levels of adherence to IECs in vitro 14, 15, and that the hair-like projections of C. difficile isolates, including isolates of the epidemically relevant 027 ribotype, have a truncated bclA1 due to a premature stop codon in the N-terminal domain 13, resulting in the translation of a small polypeptide, which localizes to the spore surface 10 thus limiting the breadth and depth of these results.Д¬. Notably, most clinically relevant sequenced C. However, the surface layer of 630 spores does not resemble that of clinically relevant strains, which exhibit hair-like projections in their spore surface, structures that are absent in strain 630 1, 11, 12. Recent in vivo studies in the laboratory strain 630 suggest that the spore-surface mucus-binding protein, peroxiredoxinвЂ“chitinase CotE, and the exosporium collagen-like BclA1 proteins are required for the colonization and infectivity in a mouse model of CDI 9, 10. difficile spores from the intestinal mucosa contribute to reducing the recurrence of the disease in animal models 8. Moreover, spore-based therapies that remove C. In vivo, spore formation is essential for the recurrence of the disease 7. difficile also initiates a sporulation pathway that leads to the production of new metabolically dormant spores in the hostвЂ™s intestine 1. difficile produces two major virulence factors, toxins TcdA and TcdB, responsible for the clinical manifestation of the disease, induce pro-inflammatory cytokines, disruption of tight junctions, detachment of intestinal epithelial cells (IECs), and loss of transepithelial barrier 6. Treatment of CDI usually involves antibiotic therapy, typically vancomycin or metronidazole and, most recently, fidaxomicin 2, which, although resolves the infection in ~95% of the cases, leads to recurrence of CDI (R-CDI) in 15вЂ“30% of the individuals 3, 4, 5.Дuring infection, C. The annual cost of CDI to the health care system is estimated at ~US 4.8 billion 2. In the US alone, ~500,000 patients per year become infected with CDI, and mortality rates reach ~8% of total patients 2. CDI currently leads hospital-acquired diarrhea associated to antibiotics in the United States and worldwide 2. difficile colonization and proliferation in the colon and disease manifestation. Disruption of the gut microbiota by broad-spectrum antibiotics leads to an optimal environment for C. difficile infections (CDI) through fecalвЂ“oral route 1. Clostridioides difficile is a strict anaerobic Gram-positive pathogenic bacterium that forms highly resistant spores that easily persist in the environment and contribute to the transmission of C.

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