Skip to main content
. Author manuscript; available in PMC: 2024 Mar 27.
Published in final edited form as: Cell Host Microbe. 2023 May 10;31(5):695–711. doi: 10.1016/j.chom.2023.03.019

Figure 1. Main mechanisms of action underlying C. difficile pathogenesis.

Figure 1.

Antibiotic-induced dysbiosis can establish a favorable condition for the germination of C. difficile spores. The vegetative form of C. difficile, thereafter, can induce pathogenesis mainly by toxin production (TcdA, TcdB, and CDT), SlpA, flagellin, and PG. C. difficile-derived PG interacts with NOD1 to stimulate neutrophil recruitment and CXCL1 production. Neutrophil infiltration and translocation to inflamed tissue result in NET formation. SlpA interaction with TLR4 can accelerate DC maturation and activation. Similar to the stimulation of TLR2 by CDT, flagellin-mediated activation of TLR5, which is promoted by TcdB, triggers transcriptional factors NF-κB and MAPK to provoke the expression of inflammatory cytokines. TcdA, however, mainly triggers programmed cell death pathways and eventually leads to apoptosis, necrosis, and pseudomembrane formation. CDT, C. difficile transferase; CXCL1, CXC chemokine ligand 1; DC, dendritic cell; MAPK, mitogen-activated protein kinase; NET, neutrophil extracellular trap; NF-κB, nuclear factor kappa B; NOD1, nucleotide-binding oligomerization domain 1; PG, peptidoglycan; SlpA, surface layer protein A; TcdA, toxin A; TcdB, toxin B; TLR, Toll-like receptor.