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. 2017 Aug 2;8:901. doi: 10.3389/fimmu.2017.00901

Table 3.

The functional enrichment analysis of the conserved target genes among three replicates based on GO terms and protein information resources of Swiss-Prot.

Category Term p-Value
Early stage
SP_PIR_KEYWORDS Metal binding 5.73E−05
SP_PIR_KEYWORD Disease mutation 0.002178622
GOTERM_BP_FAT GO:0048858~cell projection morphogenesis 0.004720934
GOTERM_BP_FAT GO:0002252~immune effector process 0.021024346
SP_PIR_KEYWORDS Tight junction 0.04930793
Late stage
SP_PIR_KEYWORDS Secreted 8.84E−04
GOTERM_BP_FAT GO:0042116~macrophage activation 0.002396512
GOTERM_BP_FAT GO:0006954~inflammatory response 0.007684734
GOTERM_BP_FAT GO:0051181~cofactor transport 0.009323758
GOTERM_BP_FAT GO:0006910~phagocytosis, recognition 0.040000612

The early stage of C. difficile infection is characterized by the change of cell shape and tight junction and this could result from the activities of GTPases and pathogen toxins. The metal-binding ability is crucial for both host and pathogen cells due to its important role in the scramble of metallic nutrients and the transport of toxic molecule, including ROS. Signaling in the case of the early stage of infection was increased for immune response, while signaling in the case of the late stage of infection was increased for the abundant cellular processes, including macrophage activation, phagocytosis, and inflammatory response. The cofactor transport and secretion-related process also contribute to the cytokine production and secretion.